tag:blogger.com,1999:blog-75357741209033848192024-03-12T19:09:33.862-07:00PossibilitiesI have the most amazing good luck. 8 years ago, my world came crashing down when my newborn baby was diagnosed with the genetic disease cystic fibrosis. Today, we feel like the most fortunate family in the world because we have Kalydeco! Now my goal is to work toward more personalized research, to help bring the most effective treatment to each and every person living with CF!Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.comBlogger70125tag:blogger.com,1999:blog-7535774120903384819.post-85146298895751867342017-11-08T19:14:00.000-08:002017-11-08T19:14:49.802-08:00NACFC 2017:Moving Gene Editing from Science Fiction to REALITY.Gene editing and mRNA editing have been discussed at NACFC for a few years now. Here is the link to <a href="http://luckycfmom.blogspot.com/2016/10/genome-editing-potential-for-cystic.html">last year's blog and conference slides</a>. Researchers have been working hard to overcome obstacles to delivery and expression of genetic treatments over the course of the last year...and they are getting somewhere. I spent Friday afternoon, as well as Saturday morning listening to talks about gene editing. Check out this animation illustrating what gene editing might look like in cystic fibrosis.<br />
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As seen in the video, nucleases can be engineered to create site specific, double strand breaks at desired locations in the genome. Antisense Oligonucleotides can be thought of as our "molecular scissors" that guide the gene editing process.<br />
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<span style="font-size: large;"><b>A First-In-Human, Phase 1B, Dose Escalation Study of QR-010, A Novel Antisense Oligonucleotide Administered in Subjects with Cystic Fibrosis Homozygous for the F508Del CFTR Mutation. </b><u>Elborn, S.</u></span></h3>
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Pro-QR is one of the companies really leading the way with gene editing technologies in cystic fibrosis, and this was a highly anticipated discussion, as this is an early gene editing trial in HUMANS WITH CYSTIC FIBROSIS. </div>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhPFjYe769yaPfYoZvJR5KCmu5E_5JVFoWwG56zjQLfHEfTtGmNhWpZfZHgHsP5bNqf6vILSxwStA6rn71H5Kc3E4SYdTLowB_eXkQimHxYE7bHGNL6oMqAWjJuRRMf5qxgGPCmpz3bMAo/s1600/20171104_113718.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhPFjYe769yaPfYoZvJR5KCmu5E_5JVFoWwG56zjQLfHEfTtGmNhWpZfZHgHsP5bNqf6vILSxwStA6rn71H5Kc3E4SYdTLowB_eXkQimHxYE7bHGNL6oMqAWjJuRRMf5qxgGPCmpz3bMAo/s640/20171104_113718.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Pro-QR's treatment is called "QR-010"</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhPX4cCsWq4upudiZZQdzpeVUXakOiXVG_uIiH611ID-PGaJgw_OLngYNYaAlYtH_EF4lXYkV1X8Q0a1zi74HO_EYo9j14zXtdKdjc4Mlv473grnqu6Qw4G4Giaayb3jPmW1IBBO0VcmYA/s1600/20171104_113727.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhPX4cCsWq4upudiZZQdzpeVUXakOiXVG_uIiH611ID-PGaJgw_OLngYNYaAlYtH_EF4lXYkV1X8Q0a1zi74HO_EYo9j14zXtdKdjc4Mlv473grnqu6Qw4G4Giaayb3jPmW1IBBO0VcmYA/s640/20171104_113727.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">An "antisense oligonucleotide" is a synthesized strand of nucleic acid that is complementary to the gene's messenger RNA.<br />Pro-QR's treatment was administered to the lungs via nebulizer.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiGBLWLRvzma8INWXuUzQIOjwJP2NZFRAnP2p5CcZ-rTTSTN5U-WfEV7DQTkqqtFaM-7h8jNfEU0-ZHZspdGzWtxvhzUVdjg04uiLY86UWycWfMzVQBe5V_yO1AsjyR0-ouWXlhiIVRWTk/s1600/20171104_113844.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiGBLWLRvzma8INWXuUzQIOjwJP2NZFRAnP2p5CcZ-rTTSTN5U-WfEV7DQTkqqtFaM-7h8jNfEU0-ZHZspdGzWtxvhzUVdjg04uiLY86UWycWfMzVQBe5V_yO1AsjyR0-ouWXlhiIVRWTk/s640/20171104_113844.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Goals are to establish safety and tolerability, as well as assess maximum tolerated dose (MTD).</td></tr>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjToThK_vDXVlKcQP4Ip_bYkzcB_LqDHUGKcFdmRa5TTbukM3utSy5l4n2SjxuJhRnZm8NtGdmIekMvl4v1BmnkcxhVzEtmcTDqPZUiA0HBcG-3TE8VuKAaYM-rYSqRuyWaCvx_0lfnXLU/s1600/20171104_114149.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjToThK_vDXVlKcQP4Ip_bYkzcB_LqDHUGKcFdmRa5TTbukM3utSy5l4n2SjxuJhRnZm8NtGdmIekMvl4v1BmnkcxhVzEtmcTDqPZUiA0HBcG-3TE8VuKAaYM-rYSqRuyWaCvx_0lfnXLU/s640/20171104_114149.jpg" width="640" /></a></div>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjo8Sjmy-bwEslMrU72nipns9JOm90STP43Zc7poSTssfphCn0SAGxAoUdXvG2l0MiMGm_6IkVwiiNFkjK4U2WAnB8v1ZAqJClcVv8Guv4AVUg34iIqNh8PMaPWpamVZ5emXoTSYVih68s/s1600/20171104_114331.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjo8Sjmy-bwEslMrU72nipns9JOm90STP43Zc7poSTssfphCn0SAGxAoUdXvG2l0MiMGm_6IkVwiiNFkjK4U2WAnB8v1ZAqJClcVv8Guv4AVUg34iIqNh8PMaPWpamVZ5emXoTSYVih68s/s640/20171104_114331.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">CFQ-R= Cystic Fibrosis Questionairre-Revised, RSS= Respiratory Symptom Score</td></tr>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgMRUOaKhzzkYPMlRD-3GN_pSC7eVmQNrYs0WjGPCbSq6hopZtPIpfhSbEmSFGKER5ED0dr-CU_siXZ7dQKYLc2aahCsFi2EYlcx0TJdDVKXJWttzbqw9lj0h7_HOPJqdrttvDC_J187Sc/s1600/20171104_114218.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgMRUOaKhzzkYPMlRD-3GN_pSC7eVmQNrYs0WjGPCbSq6hopZtPIpfhSbEmSFGKER5ED0dr-CU_siXZ7dQKYLc2aahCsFi2EYlcx0TJdDVKXJWttzbqw9lj0h7_HOPJqdrttvDC_J187Sc/s640/20171104_114218.jpg" width="640" /></a></div>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj2hSNtJ6XSGtK_tsD3-SuSEKm0XDWtpcMEaqWBim-8CzSW8MxDLtE1g37C0fF5zPy3rckdUopQDOci3NEk0nOMUPk-gbAsrk5qSwwFswj-Dondk4tD9MmKrdRc0Pe68ZfunHspz_DBhAM/s1600/20171104_114607.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj2hSNtJ6XSGtK_tsD3-SuSEKm0XDWtpcMEaqWBim-8CzSW8MxDLtE1g37C0fF5zPy3rckdUopQDOci3NEk0nOMUPk-gbAsrk5qSwwFswj-Dondk4tD9MmKrdRc0Pe68ZfunHspz_DBhAM/s640/20171104_114607.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Quality of life improvements were patient reported using the Cystic Fibrosis Questionnaire-Revised (CFQ-R), and the Respiratory Symptom Score (RSS)</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEid686Td3pW9bYZeVmNeiPs_NVa12xDIEP5TvZIH3QKRrcNjr3u1sGkG6ANQgrpMAFz8q1aHYKfDoxWXYlZb9-uniITJA8PVD9yleKAAWDXVoueo2M64RxAgUUCXvcV-dhHrSr3niYV598/s1600/20171104_114717.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEid686Td3pW9bYZeVmNeiPs_NVa12xDIEP5TvZIH3QKRrcNjr3u1sGkG6ANQgrpMAFz8q1aHYKfDoxWXYlZb9-uniITJA8PVD9yleKAAWDXVoueo2M64RxAgUUCXvcV-dhHrSr3niYV598/s640/20171104_114717.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Wow! Just Wow!!!!!!</td></tr>
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<span style="font-size: large;">Antisense Oligonucleotide-Mediated Upregulation of CFTR via Steric Block of Post-Transcriptional Control Elements: A Novel Approach for Cystic Fibrosis Therapeutics. <u>Sasaki, S.</u></span></h3>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhozH_Vxd0qbDnZKeqzvsKa6m3KulXnMgP5y0f1sxKccezFxDMl4XKQDItdXQafFcEJWDaVy-cDSoIsFXYn8Fxn5OXfZiC10cm4_QxtSPMXUeNIW2RpiRKtgoXYE1PQZaKo72_PV-GXLKQ/s1600/20171103_144651.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhozH_Vxd0qbDnZKeqzvsKa6m3KulXnMgP5y0f1sxKccezFxDMl4XKQDItdXQafFcEJWDaVy-cDSoIsFXYn8Fxn5OXfZiC10cm4_QxtSPMXUeNIW2RpiRKtgoXYE1PQZaKo72_PV-GXLKQ/s640/20171103_144651.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Antisense oligonucleotides function as our "molecular scissors."</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiftCAaoj3l_zAqDtDbNxArpJ5uUL9iwucmdw7Eg3vqucyKP4r4zBkJW1e4aqXktwdaT_lT-1Ht-kX9TxluprExXPRYwlAnUCsIErSRORTmam6iJF4eHFdjGK5rZKb00UGuDLRUyEPgiVE/s1600/20171103_144731.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiftCAaoj3l_zAqDtDbNxArpJ5uUL9iwucmdw7Eg3vqucyKP4r4zBkJW1e4aqXktwdaT_lT-1Ht-kX9TxluprExXPRYwlAnUCsIErSRORTmam6iJF4eHFdjGK5rZKb00UGuDLRUyEPgiVE/s640/20171103_144731.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Antisense oligonucleotides are programmed to target a specific site.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhr8p9LjJQCu2LE07Mwf4VwU2AxyqQPGQxPqs35TAIh_VsEfUm3H1Hy1knslB81lSfT18lvjTKYYLfQLm8Trou9d0HyNHMWZ5inLBM7-c2SOjDEsa_8Oe3Lm0569R8R5jkx68VP4fF9dv4/s1600/20171103_145133.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhr8p9LjJQCu2LE07Mwf4VwU2AxyqQPGQxPqs35TAIh_VsEfUm3H1Hy1knslB81lSfT18lvjTKYYLfQLm8Trou9d0HyNHMWZ5inLBM7-c2SOjDEsa_8Oe3Lm0569R8R5jkx68VP4fF9dv4/s640/20171103_145133.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Could this type of treatment be successful for gene transfer in CF lungs?</td></tr>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgmaImfXLvwMMwzNltSkGHNxQme7RLd8msf0ALSyCkjFO4BUwF7t4hw-9YzI1c4Hz0ubQqeYDqhoymijFBd1aAQEtKjTG2Dln3Tk6ghUXD10i-aTOe7hdw0TkFiG_hitJ3MD3pVu1AeQoI/s1600/20171103_145156.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgmaImfXLvwMMwzNltSkGHNxQme7RLd8msf0ALSyCkjFO4BUwF7t4hw-9YzI1c4Hz0ubQqeYDqhoymijFBd1aAQEtKjTG2Dln3Tk6ghUXD10i-aTOe7hdw0TkFiG_hitJ3MD3pVu1AeQoI/s640/20171103_145156.jpg" width="640" /></a></div>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgX2l5ZsTTZc8Hj4ntlEHPThPwEWbv7FbWJbDJqVa_O01GYIgBH4iHsntotzXwhnEKehwMkZDEwst6lkapdpRn42Lbq7HwRMTSsDgzpI9h08NlzqMeUb5KcYmz0RMmPORxl79YTr-7F6b8/s1600/20171103_145737.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgX2l5ZsTTZc8Hj4ntlEHPThPwEWbv7FbWJbDJqVa_O01GYIgBH4iHsntotzXwhnEKehwMkZDEwst6lkapdpRn42Lbq7HwRMTSsDgzpI9h08NlzqMeUb5KcYmz0RMmPORxl79YTr-7F6b8/s640/20171103_145737.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">ASOs = antisense oligonucleotides (our molecular scissors).</td></tr>
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<span style="font-size: large;">In Utero Nanoparticle Delivery for Site-Specific Genome Editing. <u>Ricciardi, A</u>.</span></h3>
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In 2015, researchers from Yale published a <a href="https://www.nature.com/articles/ncomms7952">study in Nature Magazine</a> where the F508del mutation was corrected in a living mouse using their specially engineered "peptide nucleic acid" (PNA) to edit the genetic defect. </div>
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<span style="background-color: white; color: #222222; font-size: 17px; letter-spacing: -0.17px; word-spacing: 0.85px;"><span style="font-family: inherit;">“What the PNA does is clamp to the DNA close to the mutation, triggering DNA repair and recombination pathways in cells,” Egan explained. </span></span></div>
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Perhaps even more importantly, the Yale group has developed a unique way to deliver their genetic treatment using nanoparticles--particles less that a billionth of a meter in diameter--designed to penetrate targeted cells. Encouraged by their success in living mice, the research group decided to try to deliver their treatment to a developing mouse embryo with cystic fibrosis. Imagine a world where cystic fibrosis could be cured before a child is even born...</div>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhAzdI2zd_sGHKeIVhEMuVKsLvtpKO4vDmFJT3HvsYu03lrZZQdE_9-bpTCglZotNP-3vv0nsS0j4Fi_zs7qrnBP_EJKk3iYncO0Fp4w1snLyPN1ea9L_zFK3yuC1dDC7Ljuv7Dk_NtRJM/s1600/20171103_150402.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhAzdI2zd_sGHKeIVhEMuVKsLvtpKO4vDmFJT3HvsYu03lrZZQdE_9-bpTCglZotNP-3vv0nsS0j4Fi_zs7qrnBP_EJKk3iYncO0Fp4w1snLyPN1ea9L_zFK3yuC1dDC7Ljuv7Dk_NtRJM/s640/20171103_150402.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">The CFF registry has confirmed that early diagnosis and intervention leads to better health outcomes.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiV5_1hFaVnED_-BNO9jG8KKdkl6jEkUMEMH42uFyaRzqdL2mHxKTC6IFVTMC9JP0aT1LQj927eEvH_4KQROsBzpHOOmJDBnnZBmwaA78qvUErHyyhi9pKnLDoGtnmgaJ2NlzMRAkCwA-8/s1600/20171103_150426.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiV5_1hFaVnED_-BNO9jG8KKdkl6jEkUMEMH42uFyaRzqdL2mHxKTC6IFVTMC9JP0aT1LQj927eEvH_4KQROsBzpHOOmJDBnnZBmwaA78qvUErHyyhi9pKnLDoGtnmgaJ2NlzMRAkCwA-8/s640/20171103_150426.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">We have the ability to detect CF in developing fetuses.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhr7l_aU4aXe9uITdGm1Ayjjoi-2pHNlohgBGrTzopf61sp5EcRNB9MKhW8stDdWdeBj3aGJNPzTfLbvFXRFYIIlshd6FIE-j4B9VsNcypl3hRJ8v1jas9eetjXJkBgaC6CZo9M6vgHwH4/s1600/20171103_150450.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhr7l_aU4aXe9uITdGm1Ayjjoi-2pHNlohgBGrTzopf61sp5EcRNB9MKhW8stDdWdeBj3aGJNPzTfLbvFXRFYIIlshd6FIE-j4B9VsNcypl3hRJ8v1jas9eetjXJkBgaC6CZo9M6vgHwH4/s640/20171103_150450.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">The fetus is deeply affected by cystic fibrosis--even prenatally.</td></tr>
</tbody></table>
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEglJDsapMOnKqKr8qyw842hcNRTXIP2QjKd4V3LNnqwELVUaWPydcGR8RRSNAiYLo8A8jFvGGgAb1nV4Bk8xRCMC2Bd5WvuN3BP2w7MDXTr6fQr8lMXAdlSVLeHQdKAWDcxqZF-wzF8GOI/s1600/20171103_150526.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEglJDsapMOnKqKr8qyw842hcNRTXIP2QjKd4V3LNnqwELVUaWPydcGR8RRSNAiYLo8A8jFvGGgAb1nV4Bk8xRCMC2Bd5WvuN3BP2w7MDXTr6fQr8lMXAdlSVLeHQdKAWDcxqZF-wzF8GOI/s640/20171103_150526.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Could in utero gene editing PREVENT cystic fibrosis altogether?!?!</td></tr>
</tbody></table>
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEine-qWPWutCWxBbCH0BDAiCsya4OIL0QYZn7Pnhhdw9BQYj0bKdSW1ucLffI-0Bx3Y7wY9KycoYNSGGvPhaBGwffGBuSDm-l6-uigtFxMwOyn6IBIG6ecoPt_HfeXe_k71nezCCvgvJMQ/s1600/20171103_150543.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEine-qWPWutCWxBbCH0BDAiCsya4OIL0QYZn7Pnhhdw9BQYj0bKdSW1ucLffI-0Bx3Y7wY9KycoYNSGGvPhaBGwffGBuSDm-l6-uigtFxMwOyn6IBIG6ecoPt_HfeXe_k71nezCCvgvJMQ/s640/20171103_150543.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Stay with me here! Remember, PNA is our pair of "molecular scissors," programmed to make the cut at a specific target.</td></tr>
</tbody></table>
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgFq3IF1iuN7-n5zkpGtO_OcA3PDHBsAvrI63JJu7galmwI-_yV04Ea26qvBsPFPnmVrQZPTKQiAa0jcMMLX8YP5maDBJOyLMqfCXD46UF-ih-0KKyWXXenRH_yR6lxiP0-o1007BRFNjE/s1600/20171103_150654.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgFq3IF1iuN7-n5zkpGtO_OcA3PDHBsAvrI63JJu7galmwI-_yV04Ea26qvBsPFPnmVrQZPTKQiAa0jcMMLX8YP5maDBJOyLMqfCXD46UF-ih-0KKyWXXenRH_yR6lxiP0-o1007BRFNjE/s640/20171103_150654.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">One of the most important things about this research is the FORMULATION of their genetic product. They do this special "nanoparticle" thing--where they cram all the genetic info onto these itty bitty spheres. </td></tr>
</tbody></table>
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgP_Co1AELY42MoGzECMU6pfwSr7tul7yu3Cm7oNbNbli86ZfXz-L0BsyMC3hEl74L3fKDJ-vOQodtL34RTrcOkKaS-byrPrFTKwa3Z85Wg77r-FIGYsCQFCI1GVPoUBzqjnO4IJfJBjww/s1600/20171103_150807.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgP_Co1AELY42MoGzECMU6pfwSr7tul7yu3Cm7oNbNbli86ZfXz-L0BsyMC3hEl74L3fKDJ-vOQodtL34RTrcOkKaS-byrPrFTKwa3Z85Wg77r-FIGYsCQFCI1GVPoUBzqjnO4IJfJBjww/s640/20171103_150807.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">The PNA/DNA nanoparticles work to correct the F508del mutation in living mice.</td></tr>
</tbody></table>
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgFOQufMkKruTXoPGzN0P6BxhjaqneJi1meURhRDoPwGxJyULQx-owK6Yc6_DK21isYt-qwaXKnEpmv6xRFBdn-wJX6PD1hDSnXkjkq_DLgyPDQFCl6ueJzyBZPmjAJK0wKmzeNABDS070/s1600/20171103_150903.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgFOQufMkKruTXoPGzN0P6BxhjaqneJi1meURhRDoPwGxJyULQx-owK6Yc6_DK21isYt-qwaXKnEpmv6xRFBdn-wJX6PD1hDSnXkjkq_DLgyPDQFCl6ueJzyBZPmjAJK0wKmzeNABDS070/s640/20171103_150903.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">So they decided to test their treatment on a developing CF mouse embryo...</td></tr>
</tbody></table>
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh2a0fZ9r-Z8L9mxK3I5T-raI1QldEa-wAOyzydG7UKco74-JubHFe4TgZR8LdtCIg6vTP_Qsqi3v_Adxr6jxV__7pJtVakNYKj8yS9JoMa4shI4m9YmmRxCSOj_KMsXOA5T1VrbV9RaXA/s1600/20171103_151013.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh2a0fZ9r-Z8L9mxK3I5T-raI1QldEa-wAOyzydG7UKco74-JubHFe4TgZR8LdtCIg6vTP_Qsqi3v_Adxr6jxV__7pJtVakNYKj8yS9JoMa4shI4m9YmmRxCSOj_KMsXOA5T1VrbV9RaXA/s640/20171103_151013.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Holy crap, is that a mouse uterus?!</td></tr>
</tbody></table>
<br />
<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiSfO1HojuKmACUlmNvaJPj2mxPY9USZwNov6MMPmhZXrajcBFa9LFT-4PAovt7ObRiAqSTLtVLcHLp62QrQ6VWaK7UpsGCJ6A3m_E41u4qXlAnJMt7KIQkTfaQhpI3wfMAsVFVtH38ees/s1600/20171103_151047.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiSfO1HojuKmACUlmNvaJPj2mxPY9USZwNov6MMPmhZXrajcBFa9LFT-4PAovt7ObRiAqSTLtVLcHLp62QrQ6VWaK7UpsGCJ6A3m_E41u4qXlAnJMt7KIQkTfaQhpI3wfMAsVFVtH38ees/s640/20171103_151047.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Researchers have to use specially made glass pipettes to inject their nanoparticles into this particular vein in the uterus.</td></tr>
</tbody></table>
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgyVdpokmshhRjuHji7-1yK61Tuc157J2-Z09DRc2SnOYYIuxMrOPFt_m0NtXsj7WH1l2UTpCBJX3EGCd6n7_kW6lGSHXfMae-NsC37SmsoQjsNcYMTLryMHB5XniyPmHnjyMhBwM3bybE/s1600/20171103_151200.mp4" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgyVdpokmshhRjuHji7-1yK61Tuc157J2-Z09DRc2SnOYYIuxMrOPFt_m0NtXsj7WH1l2UTpCBJX3EGCd6n7_kW6lGSHXfMae-NsC37SmsoQjsNcYMTLryMHB5XniyPmHnjyMhBwM3bybE/s640/20171103_151200.mp4" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">So cool. This is the actual injection of the nanoparticles into the uterine vein.</td></tr>
</tbody></table>
<div class="separator" style="clear: both; text-align: center;">
</div>
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg5I7Jjqmtb_hjZ5sgFNHnFSoO7n42J91-A0xelkxpM3nc6uelOBIz3wzdJ8cI07ZxdiQ3sBrdTHObYGu-wsF7OjDoTW6EFvbhXmoMXyOBLWsM6dxY5O03NhFUFpuCnVT-QEc4nuEG6IeM/s1600/20171103_151320.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg5I7Jjqmtb_hjZ5sgFNHnFSoO7n42J91-A0xelkxpM3nc6uelOBIz3wzdJ8cI07ZxdiQ3sBrdTHObYGu-wsF7OjDoTW6EFvbhXmoMXyOBLWsM6dxY5O03NhFUFpuCnVT-QEc4nuEG6IeM/s640/20171103_151320.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Researchers were able to show uptake and expression of desired genetic information in fetal organs!!!</td></tr>
</tbody></table>
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi_QrhLlrMUqHhbNqhFTgBuzNX7DSeRBGyZpls7WnacSaJ3jT10d3gNEKXovIGd3P7FenVZjHlKKE6kHri3MtQxWCCEzfI44AUhWfPxbNOlP3yIlYhLS4U5k5NK_hNbNgigouUqueE7Wgs/s1600/20171103_151335.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi_QrhLlrMUqHhbNqhFTgBuzNX7DSeRBGyZpls7WnacSaJ3jT10d3gNEKXovIGd3P7FenVZjHlKKE6kHri3MtQxWCCEzfI44AUhWfPxbNOlP3yIlYhLS4U5k5NK_hNbNgigouUqueE7Wgs/s640/20171103_151335.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">In conclusion...holy shit. This talk left my jaw hanging open!</td></tr>
</tbody></table>
<h3>
<span style="font-size: large;"><br />Manipulating Vector Interactome to Enhance Gene Delivery. </span><u><span style="font-size: large;">Siefert, M</span>.</u></h3>
As previously noted, perfecting the "vector" to enhance gene delivery was a hot topic because it has proven to be so challenging over the years.<br />
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<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiHPaKJ8ZtQHZPRKXy0WzGXjKnfSYsP1FxGIGMFEnUCZTPZeXz8lI3NHksWDXA5TGzlX3KaNs5hQpgmIAFqkZTS_7-mD-f9NJrVydS455BfNIEJfI0KG0exHk3R8b7RVmoyCPm3pwTw3J4/s1600/20171104_104732.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiHPaKJ8ZtQHZPRKXy0WzGXjKnfSYsP1FxGIGMFEnUCZTPZeXz8lI3NHksWDXA5TGzlX3KaNs5hQpgmIAFqkZTS_7-mD-f9NJrVydS455BfNIEJfI0KG0exHk3R8b7RVmoyCPm3pwTw3J4/s640/20171104_104732.jpg" width="640" /></a></div>
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg9jSMgvWrKyTg-niNpQjg7S1HRAhWoLpX3E4zjW3bWthGj6llyGgZR7PsNDvmbTIQZ93UjE8tq8UJsLzrKb2qaSFwoqwj6g1kDLR04SdsuV49pJlXlzvJ6ea9vqtrl4VDuf2Zubibq1xc/s1600/20171104_104835.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg9jSMgvWrKyTg-niNpQjg7S1HRAhWoLpX3E4zjW3bWthGj6llyGgZR7PsNDvmbTIQZ93UjE8tq8UJsLzrKb2qaSFwoqwj6g1kDLR04SdsuV49pJlXlzvJ6ea9vqtrl4VDuf2Zubibq1xc/s640/20171104_104835.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Researchers have encountered multiple obstacles to success gene transfer.</td></tr>
</tbody></table>
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<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEikKBg_DSJIv24aog1LAcYJkB_RHjeuI83lGUf6zxQsrqRubF6Qb3z0AJvouj4fK3t3uaGDLKqtf4JFndYhWZTyQ-eZCzt2Syz5LjxgOJ7zoFWh01NYVtly-mdq78dAWeeIQPeR61EEtj4/s1600/20171104_104907.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEikKBg_DSJIv24aog1LAcYJkB_RHjeuI83lGUf6zxQsrqRubF6Qb3z0AJvouj4fK3t3uaGDLKqtf4JFndYhWZTyQ-eZCzt2Syz5LjxgOJ7zoFWh01NYVtly-mdq78dAWeeIQPeR61EEtj4/s640/20171104_104907.jpg" width="640" /></a></div>
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjgSB_Q9TFafwQXwR7fFFeMs3Nw_1AQUqFZY3OJW5yeoDgm7Y-hfPbzXKUhDM5OzdC_Gw9KadfqD-S19pImuKEbr2QMNPTrnPdSOQk06Z5YLmnWKFymzfd7V1lSfpA9avMWwjtto-mqi8g/s1600/20171104_104951.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjgSB_Q9TFafwQXwR7fFFeMs3Nw_1AQUqFZY3OJW5yeoDgm7Y-hfPbzXKUhDM5OzdC_Gw9KadfqD-S19pImuKEbr2QMNPTrnPdSOQk06Z5YLmnWKFymzfd7V1lSfpA9avMWwjtto-mqi8g/s640/20171104_104951.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Another example of nanoparticle delivery. Could this be the way forward?</td></tr>
</tbody></table>
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<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi0fvWYojPQZJlj_tjHYCNzqe2HwPh1GTCw_AsA2R6FRAQuE5E6Kax77b7_aeJ0xMgk3Kbx5tAlqrfItE9xFd0Ehoy1_ewok4c3H-wnmmX0vSXju51lm6Iky1KOc4W_fa88G97qQcqGc78/s1600/20171104_105026.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi0fvWYojPQZJlj_tjHYCNzqe2HwPh1GTCw_AsA2R6FRAQuE5E6Kax77b7_aeJ0xMgk3Kbx5tAlqrfItE9xFd0Ehoy1_ewok4c3H-wnmmX0vSXju51lm6Iky1KOc4W_fa88G97qQcqGc78/s640/20171104_105026.jpg" width="640" /></a></div>
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgYr7UMWb8naf0iqefz6EFf6lfe21OQ1qkSPNiUJ3WGpCVvPCDah9cbdve46qSoxMNb11ovDLl2dLpx2VJWX9et45CIbEKl3hnZoBsCSsmxacNG_Np6fih1CwMLUPYa6QGmGL_x5fle634/s1600/20171104_105119.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgYr7UMWb8naf0iqefz6EFf6lfe21OQ1qkSPNiUJ3WGpCVvPCDah9cbdve46qSoxMNb11ovDLl2dLpx2VJWX9et45CIbEKl3hnZoBsCSsmxacNG_Np6fih1CwMLUPYa6QGmGL_x5fle634/s640/20171104_105119.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Safe, but not perfect.</td></tr>
</tbody></table>
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgYkMXsnxTV49pxX174KNJehP5JMLfzSXRKK3EqtPacItZ11w_-AsRpL7a7vZOWKftCznfsSg1k8pxFAxdYTKrNlxic4ARhPP-BBLSH5y0kuxbMvkVu5WMdTWCsaJb4Kou66DRgpYzofNg/s1600/20171104_105157.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgYkMXsnxTV49pxX174KNJehP5JMLfzSXRKK3EqtPacItZ11w_-AsRpL7a7vZOWKftCznfsSg1k8pxFAxdYTKrNlxic4ARhPP-BBLSH5y0kuxbMvkVu5WMdTWCsaJb4Kou66DRgpYzofNg/s640/20171104_105157.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">How do we improve efficacy?</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgeqwAENvxdLymXruI4t1D8ucqoTK-_p26TYtGKiPApwHR__2Et5_SPsTCfpnvqzdZ7F6zALW8KaOHZMDQlcd3gaHO1YVddyCYj0hM7M3sgPMz0Di3_1k474JdUq0AShuHH4mK0UAQESN8/s1600/20171104_105224_001.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgeqwAENvxdLymXruI4t1D8ucqoTK-_p26TYtGKiPApwHR__2Et5_SPsTCfpnvqzdZ7F6zALW8KaOHZMDQlcd3gaHO1YVddyCYj0hM7M3sgPMz0Di3_1k474JdUq0AShuHH4mK0UAQESN8/s640/20171104_105224_001.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Penetrating mucus is a formidable barrier in CF.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg72Bu-JwTMxEXV6fVh5CcmLJCJlApLjvj3PpwaFULtd_eKu8wLsDXTEgbL_d_ULENdLbPh0G-3v7hThGC9_2DzXeMrEKCvK7JOmlAEHGC-vQIm_bWoRtG_1bgwVTPL51C3E1xRCJ_EIFE/s1600/20171104_105355.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg72Bu-JwTMxEXV6fVh5CcmLJCJlApLjvj3PpwaFULtd_eKu8wLsDXTEgbL_d_ULENdLbPh0G-3v7hThGC9_2DzXeMrEKCvK7JOmlAEHGC-vQIm_bWoRtG_1bgwVTPL51C3E1xRCJ_EIFE/s640/20171104_105355.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Manipulation of other cellular interactions can enhance gene transfer.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjqX_6f76MJQKhyphenhyphenKQGNmTDSeNYTM0Sf-1pv0rzJBIrToFwhHp2aL9aomyjCfqxWK1gk5UO3mZN-SZ8OKeNSXrGXh_YChkJbIQc-snRN73X_iBxBu_-AhwRlyMMtZiP2aTGoLwoQt1H0FPw/s1600/20171104_105430.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjqX_6f76MJQKhyphenhyphenKQGNmTDSeNYTM0Sf-1pv0rzJBIrToFwhHp2aL9aomyjCfqxWK1gk5UO3mZN-SZ8OKeNSXrGXh_YChkJbIQc-snRN73X_iBxBu_-AhwRlyMMtZiP2aTGoLwoQt1H0FPw/s640/20171104_105430.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">It is worth taking a closer look at how to achieve maximal benefit from manipulation of these cellular interactions.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgIp3sYUVMtq7nmB1ZFfHRSmds-jCRwQFyUvqnaYTxftIxgEY11Kzkk7jJnLyE6dbFzMdeShTRimbdkds5PESp0XP_X-wUaa0FRf-i1iVbNihYZFpCLa5oaauiNZmP8WCwhSR1gBkVRcV8/s1600/20171104_105727.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgIp3sYUVMtq7nmB1ZFfHRSmds-jCRwQFyUvqnaYTxftIxgEY11Kzkk7jJnLyE6dbFzMdeShTRimbdkds5PESp0XP_X-wUaa0FRf-i1iVbNihYZFpCLa5oaauiNZmP8WCwhSR1gBkVRcV8/s640/20171104_105727.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Researchers were able to show improved efficacy of their gene product by manipulation of cellular interactome.<br /><span style="font-size: large;"><br /></span><div style="text-align: left;">
<span style="font-size: large;">What an amazing world we live in. Cure Cystic Fibrosis.</span></div>
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Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com6tag:blogger.com,1999:blog-7535774120903384819.post-67606642470924142952017-11-07T07:37:00.001-08:002017-11-07T07:37:05.837-08:00NACFC 2017--Forward Progress for Next Generation Modulator Combos and Treatment of Rare MutationsThis is my 7th year attending the NACFC...and after 3 days of Workshops, Symposia, and Plenary Sessions--I am more optimistic than ever. At the NACFC, I try to take every opportunity I can to soak in the science and connect with the researchers. This year was the largest NACFC ever--with close to 5000 in attendance from all over the world. I skip the gym, sleep, and regular meals to that no opportunities escape me. This entry will touch on exciting news from the first Plenary Session.<br />
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<b><span style="font-size: large;"> 2020 is going to be a BIG year for treating Cystic Fibrosis</span></b><br />
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The first Plenary Session always features the most exciting progess from the previous year. I've been watching and writing about the development of the "second generation" 3 drug combinations of CFTR modulators at NACFC for several years. The lab data has been nothing short of THRILLING. Finally, researchers are confident enough in the combounds that they've put a real timeline on moving these breakthroughs from the lab to your medicine cabinet. The second generation combos will be available for those with either one or two copies of F508del, which means that 90% of the CF population will be eligible for treatment in 2020!<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg4HW1NxBEg-O-lEuuAHODqqvFIVTjoFwltxArGDBP5SN2CHvwaTmR-JKu-L3hvW4_MF7nXgLv6EyMB68rEcvKS8WcEf_cdOk6ZH_x_V4b9zxrj-ryilcxwjozNbN5blYIMenoFH8UyrG4/s1600/20171102_173154.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg4HW1NxBEg-O-lEuuAHODqqvFIVTjoFwltxArGDBP5SN2CHvwaTmR-JKu-L3hvW4_MF7nXgLv6EyMB68rEcvKS8WcEf_cdOk6ZH_x_V4b9zxrj-ryilcxwjozNbN5blYIMenoFH8UyrG4/s640/20171102_173154.jpg" width="640" /></a></div>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEghO0uvT1CbSfK43AnJVzrUyizZTTC-nfuHOGVgkziDTF_hq-2TXcjBCNqQX6IZPMLKr8RTbbJeCIdZ2iA9IOynYT0xSLhGbplIuR9HFlbKbqh03hWG5GAKw3p8uJkPTUVoM5ATkemAJR8/s1600/20171102_173322.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEghO0uvT1CbSfK43AnJVzrUyizZTTC-nfuHOGVgkziDTF_hq-2TXcjBCNqQX6IZPMLKr8RTbbJeCIdZ2iA9IOynYT0xSLhGbplIuR9HFlbKbqh03hWG5GAKw3p8uJkPTUVoM5ATkemAJR8/s640/20171102_173322.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">CFTR response for homozygous F508del--INCREDIBLE!</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjG3geSceFqpNEWRe7DtEvtEK6I847B4HlIbj48WdhhULnZijTF4Nk4UiTjv7XnUMa-kp3KA5-2hiW8sNSXiqvoLW76TstMHUdhD_yhip796JQ6PKFE4-AHy-7pXQdbyq1aoXQAgcXFCPk/s1600/20171102_173359.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjG3geSceFqpNEWRe7DtEvtEK6I847B4HlIbj48WdhhULnZijTF4Nk4UiTjv7XnUMa-kp3KA5-2hiW8sNSXiqvoLW76TstMHUdhD_yhip796JQ6PKFE4-AHy-7pXQdbyq1aoXQAgcXFCPk/s640/20171102_173359.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">CFTR Response to next gen combos for heterozygotes with one F508 del mutation. Treating one mutation alone offers a clinical response almost as good as Kalydeco for G551D.</td></tr>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgOeR_c8EZ7En8di5u4q_NUTc9CrY288taS4u11EVP-RlCMNx6Vt05H3_Pky03YlULGVRGxCrufpAOOLkB2ydAs7qkN7OPsG_oiiv6_irVhD3h04WWCxRz1QCQm4wovnW60mfq4yn_IhDg/s1600/20171102_173555.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="900" data-original-width="1600" height="358" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgOeR_c8EZ7En8di5u4q_NUTc9CrY288taS4u11EVP-RlCMNx6Vt05H3_Pky03YlULGVRGxCrufpAOOLkB2ydAs7qkN7OPsG_oiiv6_irVhD3h04WWCxRz1QCQm4wovnW60mfq4yn_IhDg/s640/20171102_173555.jpg" width="640" /></a></div>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiBtYe_1caH5inGHJXxACAImK_tkXY7DYuey59l1xbAX3Vm5YBK4mUk-Vrj42LEx3VdbPbZFkv_jA4EVka-0GodU1BTzQrFx0u5WW_tfv0XB6yY5BzrzwXmcF7t3ZF-zeJva6zzHMQlVd8/s1600/20171102_173530.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiBtYe_1caH5inGHJXxACAImK_tkXY7DYuey59l1xbAX3Vm5YBK4mUk-Vrj42LEx3VdbPbZFkv_jA4EVka-0GodU1BTzQrFx0u5WW_tfv0XB6yY5BzrzwXmcF7t3ZF-zeJva6zzHMQlVd8/s640/20171102_173530.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Studies focused on selection of the best of the Vertex corrector in development (the 3rd ingredient in our cocktail) to add to the next gen combo.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhy2LQ_wXF8VDRwyAsxcB00qsofU_d3DK9S7KSY8mUG_0v2tNdR7uxnlw4dr1YkQWUSSucC4bRgzUJlEgJTLS03mQAhezoxvi8iyl24pBfC2f59KkJNycm1JK9gWr5ODQW3CbSaSWeZtZ8/s1600/20171102_174048.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhy2LQ_wXF8VDRwyAsxcB00qsofU_d3DK9S7KSY8mUG_0v2tNdR7uxnlw4dr1YkQWUSSucC4bRgzUJlEgJTLS03mQAhezoxvi8iyl24pBfC2f59KkJNycm1JK9gWr5ODQW3CbSaSWeZtZ8/s640/20171102_174048.jpg" width="640" /></a></td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjYau0w-b6TpcJ-ITxuQlFzF1bjBdLuFTDWeSU3ExMj4x75UbCyVvNDlKA3DFBU8M_Vg1ItF8QBlkvcbRD7wyuJGbCRvt5wUg6pz5ka2wYOoa77gicP4ZRGJFF6cYs8V3f04bvTxcQmO_s/s1600/20171102_173909.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjYau0w-b6TpcJ-ITxuQlFzF1bjBdLuFTDWeSU3ExMj4x75UbCyVvNDlKA3DFBU8M_Vg1ItF8QBlkvcbRD7wyuJGbCRvt5wUg6pz5ka2wYOoa77gicP4ZRGJFF6cYs8V3f04bvTxcQmO_s/s640/20171102_173909.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">The CFF is leaving no stone unturned to effectively treat nonsense mutations.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiR-68s00m7rYEBQ4EFIwY_lufVG4SQGkcqtBUu2vim4lvXp7qC9dm0LGidRR_dH0_53T5czNLC24KRtSvPVU4PWxMBc_AggeP-YK3qTFEF3Nf9lovGRjujRp6pqEql33X9DsQo6XnEsX4/s1600/20171102_173935.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiR-68s00m7rYEBQ4EFIwY_lufVG4SQGkcqtBUu2vim4lvXp7qC9dm0LGidRR_dH0_53T5czNLC24KRtSvPVU4PWxMBc_AggeP-YK3qTFEF3Nf9lovGRjujRp6pqEql33X9DsQo6XnEsX4/s640/20171102_173935.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Gene editing or mRNA editing represents a true opportunity for a one time cure for people with ANY of the thousands of cystic fibrosis mutations.<br />
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<b><span style="font-size: large;">FDA Accepts Lab Data as Legitimate Path Toward Drug Approval for Rare CF Mutations.</span></b></div>
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There are over 1000 mutations of cystic fibrosis worldwide that are only carried by a very small number of individuals. The potential to perform a traditional large scale human trial does not exist. As treatments for those with cystic fibrosis evolve, so must the FDA's approval criteria. I am so encouraged by this step forward. We now have the capability to test drug responses in cell lines in the lab, and truly personalize medicine for people with rare mutations. There are many that may even be responsive to existing drugs like Kalydeco, and now we have the opportunity to make sure responders are not getting missed! </div>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhDFCXvf3HFApjT6vtTKaPnTURuygAcapfptCyDJae7YzbkfGhTkSnLf5_Nb8n3v0ZLcryOPxQbxFdinpRDIq0vNpJi1wY8RRJcMNNBrYiBniAmFpBedOtVLkQDnP0ar_PQpfySAnsFQno/s1600/20171102_172451.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhDFCXvf3HFApjT6vtTKaPnTURuygAcapfptCyDJae7YzbkfGhTkSnLf5_Nb8n3v0ZLcryOPxQbxFdinpRDIq0vNpJi1wY8RRJcMNNBrYiBniAmFpBedOtVLkQDnP0ar_PQpfySAnsFQno/s640/20171102_172451.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">The FDA is an integral part of getting drugs to patients. This evolution of the drug approval process is a huge step forward!</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjtAn51i3_L96POHqGJfl719wL8CyP1Znk0uJ_6dw2xgSozcsGYXtQnQoTPHNWiSDfNKALcy5P-psRBDjYa57w1FvMNO8wccnOqi2F-lqX9oEq-t5ZvUkMLMR9Kj_-drTNosAbLu1LeZ8A/s1600/20171102_175250.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjtAn51i3_L96POHqGJfl719wL8CyP1Znk0uJ_6dw2xgSozcsGYXtQnQoTPHNWiSDfNKALcy5P-psRBDjYa57w1FvMNO8wccnOqi2F-lqX9oEq-t5ZvUkMLMR9Kj_-drTNosAbLu1LeZ8A/s640/20171102_175250.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">It would be horrible to be missing out on an existing treatment if your mutation would benefit.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjhlyNZIhT__T7AgQ1qoUv2LEONcLPweqd96xgvfissP5AOlAL-sy445Y5Ujz6syQcb01TZNfYLiWkLdBtwJOYK0o89JRXzkHDdZ4s_GcyueeaeXcANPfDOJdNu9v6b-AHoSSb7XxyeKKM/s1600/20171102_175601.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjhlyNZIhT__T7AgQ1qoUv2LEONcLPweqd96xgvfissP5AOlAL-sy445Y5Ujz6syQcb01TZNfYLiWkLdBtwJOYK0o89JRXzkHDdZ4s_GcyueeaeXcANPfDOJdNu9v6b-AHoSSb7XxyeKKM/s640/20171102_175601.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Testing drugs on cell lines in the lab in a way to bypass large scale clinical trials for those with rare CF mutations.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgLi6OkY9iuiSXOoOwJh0v6yF3tabLNKoe254551stq2WSbx9QSLW-m2kOidlPRiujXKyaYBOywaqh4lakayk79HdCKc6Ay5TKhlJbT1GU8HBofRRkSQMIO2SqPyPQibWX0oWYRa04RnBU/s1600/20171102_180105.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgLi6OkY9iuiSXOoOwJh0v6yF3tabLNKoe254551stq2WSbx9QSLW-m2kOidlPRiujXKyaYBOywaqh4lakayk79HdCKc6Ay5TKhlJbT1GU8HBofRRkSQMIO2SqPyPQibWX0oWYRa04RnBU/s640/20171102_180105.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">There is an effort underway to evaluate rare mutations to better predict drug response.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiRPvExRQAn0MnRQrjFvJSLKs8dU0OWUMcPfR_LU7bZgo0SCqvshylvc5jaz7xxJR_6mrdhWgxvXsAYmX_kkEtCg_LO5bBL0lUL86a6S0eOLr-PlW7jSLGD_uwnsKVVajf9fxyF6oUrBqY/s1600/20171102_181528.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="900" data-original-width="1600" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiRPvExRQAn0MnRQrjFvJSLKs8dU0OWUMcPfR_LU7bZgo0SCqvshylvc5jaz7xxJR_6mrdhWgxvXsAYmX_kkEtCg_LO5bBL0lUL86a6S0eOLr-PlW7jSLGD_uwnsKVVajf9fxyF6oUrBqY/s640/20171102_181528.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Techniques to address the mutations not eligible for small molecule modulators.</td></tr>
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LEAVE NO ONE BEHIND.</div>
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Next entry will focus on GENE EDITING!</div>
Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com3tag:blogger.com,1999:blog-7535774120903384819.post-54127625495914336472017-04-27T07:49:00.002-07:002017-04-27T08:26:15.298-07:00The Case for CompassionIronically--fighting for healthcare may stress me to death. I'm struggling to stay positive, but it helps to know I'm not alone. My Mama Bear Defense System is humming at full throttle. I'm anxious, and frequently on the edge of tears... I'd love to just take a vacation and check out, but now is not the time to take our eyes off the ball in terms of advocating for healthcare policy for those with cystic fibrosis.<br />
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The CF community engaged with lawmakers in a formidable way in opposition to the GOP's American Health Care Act (AHCA), providing feedback about the inadequacies of the legislation with over 34K calls, texts, and emails tracked through the CF Foundation's advocacy platorm. These interactions MATTER. Because of the overwhelming public outcry to the bill, the Republican party wasn't able to unite in support, and the legislation never even saw the light of day for a vote in the House. Read about the original legislation and the impact it would have on those with CF <a href="http://luckycfmom.blogspot.com/2017/01/the-policy-punchline.html">here</a>. <b>All of the concerns with the original legislation still remain. The cuts to Medicaid are still intact in this amended legislation, and would be devastating to millions.</b><br />
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<u><b>ROUND 2</b></u><br />
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I was incredibly relieved when the AHCA was pulled from the House floor prior to a vote, but the GOP is geared up to take another shot at passing the AHCA with a new amendment. The amendment is designed to appeal to the two factions of the Republican Party that blocked the passage of the legislation the first time around.<br />
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<b>1)</b> Moderate Republicans represented primarily by "<a href="https://en.wikipedia.org/wiki/Tuesday_Group">The Tuesday Group</a>" in the House.<br />
<b>2)</b> Ultra Conservative Rebulicans represented primarily by the House "<a href="https://en.wikipedia.org/wiki/Freedom_Caucus">Freedom Caucus</a>."<br />
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Moderate Republicans from The Tuesday Group say they would have voted no on the legislation if they had the opportunity, due to the negative impact it would have on the people who vote for them.<br />
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The Freedom Caucus members, however, say they would have voted NO to the legislation for a very different reason. They want to pull the bill much further to the right--stripping away protections for people with pre-existing conditions. Their idea is to allow insurers to discriminate agains those with health conditions and charge them more $$$--which forces patients into state run high-risk pools (which have been shown over decades to be disastrously inadequate). The Freedom Caucus also wants to allow insurers to reduce their standard of "essential benefits" covered in plans.<br />
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<u><b>THE AMENDMENT</b></u><br />
The amendment to the AHCA makes the bill much MORE DANGEROUS for people with cystic fibrosis--or any other health condition for that matter.<br />
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<span style="background-color: white; color: #1d2129; font-family: "helvetica" , "arial" , sans-serif; font-size: 14px;"><a href="http://www.politico.com/story/2017/04/20/obamacare-repeal-republicans-new-deal-237397">"the latest proposal would allow states to apply for "limited waivers" that would undermine Obamacare's protections for pre-existing conditions. Under these waivers, states could opt out of Obamacare standards setting minimum benefits that health plans must offer and a requirement — called community rating — forbidding insurers from charging different prices to people based on health status."</a></span><br />
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The amendment to the AHCA would give states the ability to opt-out of Obamacare standards--which is exactly what my Congressman Raul Labrador--Leadership of the Freedom Caucus wants to see. In a Town Hall a few days ago, Rep. Labrador said:<br />
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For those with complex chronic health conditions like Cystic Fibrosis, health insurance must actually COVER HEALTH CARE to be effective. Losing protections for those with pre-existing conditions and lowering the level of essential health benefits that insurers must cover may sound alright to Labrador on paper...but the policies would be "CATASTROPHIC" to actual people. Labrador believes that people with health conditions should absolutely be forced to pay more for their insurance, and wants to bring back high-risk pools as the best method of dealing with the "less than healthy." There are decades of experience with high-risk pools to illustrate the inadequacy of this option. Returning to the discrimination of high-risk pools would be a huge step backward.<br />
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<u><b>THE CASE FOR COMPASSION</b></u><br />
I can argue about policy until I'm blue in the face. It is much much harder for me to argue about compassion. In discussing healthcare face-to-face with Congressman Labrador in early March, he spoke about his desire to make our healthcare system "fair" to the young healthy 20 year olds who he believes are paying "too much" for insurance. I completely understand that not everyone requires the same high standard of care that those with CF need, but I also think it is extremely narrow-sighted to design a healthcare system around the individuals that DON'T NEED IT as the #1 priority. The changes proposed in the latest amendment to the already awful AHCA would do the greatest harm to children, the disabled, and the elderly--the most vulnerable in our society. What can I say to convince Labrador (and others) that it is not OK to let people suffer and/or die because they can't access the care that they need? Are we plunging into a "survival of the fittest" scenario here in the US, where there is no room for compassion? Can we actually stomach systematic discrimination against those with serious health conditions in this nation and watch this tragedy unfold with eyes wide open? The <a href="https://www.washingtonpost.com/opinions/apparently-repealing-obamacare-could-violate-international-law/2017/04/25/2794a77c-29f4-11e7-b605-33413c691853_story.html?utm_term=.429de57bd8d3">United Nations has even stepped in to warn the administration that taking away healthcare from 30 million Americans without a suitable replacement would represent both a violation of human rights, as well as binding international conventions. </a><br />
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Individuals with pre-existing conditions are <b><i>people</i></b> with families, talents, and dreams...just like my precious Brady. This legislation would put America behind nearly every other developed nation in the world in terms of healthcare for our citizens. We can do SO MUCH BETTER, and we must demand that Congress go back to the drawing board. Interestingly, <a href="http://www.vox.com/2017/4/25/15429982/gop-exemption-ahca-amendment">Congress has decided to exempt themselves from the most dangerous aspects of this legislation</a>. We mustn't let hypocrisy win. Please call your member of Congress today and ask them to OPPOSE the AHCA. The CFF's advocacy action center is the easiest possible way to make those connections with lawmakers. Don't wait--follow the link to <a href="https://authoring.cff.org/Get-Involved/Advocate/Current-Advocacy-Actions/Tell-Congress-to-Protect-Your-Coverage/">take action NOW</a>!<br />
<br />Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com1tag:blogger.com,1999:blog-7535774120903384819.post-15210116359066565822017-01-08T12:55:00.000-08:002017-01-08T18:34:20.197-08:00The Policy PunchlineAs National Advocacy Co-Chair for the Cystic Fibrosis Foundation (with my fabulous Co-Chair Melissa Shiffman), and Mother to a 9 year old living with cystic fibrosis, my level of anxiety has been elevated to some all new heights as the dismantling of our healthcare policy looms on the horizon. A second contributor to my overall mental health crisis is the INCREDIBLE LACK OF DETAIL about what will be proposed to replace the ACA. By all sources, the 1st order of business for the incoming administration will be the repeal of large portions of the Affordable Care Act ("Obamacare"). The ACA is an incredibly large and complex piece of legislation--for the purposes of this discussion, I will focus on the portions that most deeply impact those living with chronic diseases like cystic fibrosis. Whether or not healthcare policy is really your cup of tea, it is going to be crucial for us to UNDERSTAND and FIGHT for access to affordable and adequate healthcare and medicine as new legislation is proposed in this new era. We certainly can't afford for our needs to be boiled down to "one-liners" or lost in a jumble of confusing rhetoric. Let's detail a few of the conversations we will need to be a part of to ensure that those with CF have access to adequate and affordable healthcare coverage, accredited CF care centers, and the most effective medications. I encourage you to read the <a href="https://www.cff.org/CF-Community-Blog/Posts/2016/A-Message-to-the-Community-Following-the-Election/">CFF's message to the community following the election.</a><br />
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<u><b>The Affordable Care Act ("Obamacare")</b></u><br />
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Certain portions of the ACA are highly relevent to promoting insurance coverage and high quality care for those with CF.<br />
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<b><u>Lifetime and Annual Benefits Caps</u></b><br />
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Unless you have personally approached a lifetime or annual benefits cap (prior to the ACA), this issue may not be on your radar--BUT IT ABSOLUTELY SHOULD BE NOW. Before Obamacare, insurers set a cap on the amount of benefits they would pay out to an individual in a single calendar year, and also set a lifetime cap on the benefits paid on an individual plan. The annual caps varied from policy to policy, but the lifetime caps were typically set between $1-2 million. The ACA prohibited insurers from setting these annual and lifetime insurance caps. </div>
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<a href="https://www.hhs.gov/healthcare/about-the-law/benefit-limits/index.html">https://www.hhs.gov/healthcare/about-the-law/benefit-limits/index.html</a></div>
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The policy that my family held prior to the ACA was a great plan purchased through my husband's employer with a $2 million dollar cap. Over the course of the last 8 years, successful research endeavors have changed the direction of treatment for CF. For example, the last time these caps were legally allowed, KALYDECO AND ORKAMBI DID NOT EXIST. Those with CF undergoing transplant were likely to encounter these lifetime/annual caps at the most critical time in their care, and I hope that some who've experienced this will be kind enough to leave a comment about how this affected them. </div>
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Today, we are fortunate enough to be in an era of greater understanding and treatment of the root cause of cystic fibrosis with small molecule gene modifiers. I am acutely aware that not everyone with CF is able to benefit from a drug like Kalydeco or Orkambi right now, but the drug development pipeline is absolutely packed with compounds that are poised to move to market in the coming years. Upcoming gene modifiers are anticipated to carry the same level of "ultra-premium pricing" as Kalydeco and Orkambi. Let's break down the math for someone like my 9 yr. old son Brady--who depends on Kalydeco (among many other prescriptions!) to stay healthy.</div>
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Monthly Rx of Kalydeco = $34K</div>
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$34K x 12 months = $408K annually </div>
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$2,000,000 lifetime cap divided by $408K/year = 4.9 years of benefits before reaching cap</div>
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Effectively, reaching a lifetime max on benefits would take less than 5 years for someone like my son Brady with that single Rx. Kalydeco has been an incredible life changing drug for him since the day he began treatment (Feb. 10th, 2012--which equates to 4 years and 11 months of prescription benefits). Without the protections outlined in the ACA, he would MAX OUT HIS <b>LIFETIME </b>INSURANCE BENEFITS THIS MONTH (as we just tipped over the $2 million dollar mark) with that drug alone (not counting enzymes, antibiotics, breathing treatments, etc...)<b>!!!</b> I want to reiterate that Brady is 9 years old, and the prescriptions he takes have allowed him to live a full healthy life. Along the same lines, any <b>annual </b>caps (which would be much lower) placed on benefits could potentially be maxed out by filling a single month's worth of a drug like Kalydeco or Orkambi! </div>
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Those needing an organ transplant or spending significant amounts of time hospitalized would also be deeply affected by these caps. How would you feel if your insurance benefits were simply cut-off when you reached their pre-determined max? What would you do? If that doesn't make you stop and think long and hard about the future of caring for cystic fibrosis--I don't know what will. Allowing lifetime and annual caps to return and be legally instituted by insurers will absolutely--no doubt about it--be a deadly disaster for those with chronic diseases like CF. Until we cure CF, the thought of "part-time" coverage because of annual caps, or maxing out your lifetime of benefits in just a few years is not a scenario we want to see become a reality. CF is a chronic disease that requires high quality chronic treatment. Allowing these caps to be put back into place will effectively flush our progress toward treatment of this disease down the toilet, because access to drugs and therapies will be governed by insurance caps on benefits. Let's be clear that simply gaining FDA approval for new incredible drugs does NOT GUARANTEE ACCESS. My hands are trembling just typing this...</div>
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<u><b>Pre-existing Conditions</b></u><br />
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If you were born with cystic fibrosis--you are likely aware that you have what insurers call a "Pre-existing Condition"...but did you know that the Affordable Care Act provides 3 SEPARATE and EQUALLY IMPORTANT protections for those with pre-existing conditions?</div>
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1) Insurers cannot refuse sale of a policy to those with pre-existing conditions.</div>
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2) Insurers cannot charge these individuals more $$$ for their policy.</div>
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3) Insurers cannot "carve out" coverage for those with pre-existing conditions. (**For example, before the ACA, it was legal for an insurer to sell a policy to someone with CF, but exclude all coverage relating to the treatment of the disease).<br />
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I hope it is clear pre-existing protections #2 and #3 are just as vital as #1. What good would it do to have the legal option to purchase a health insurance plan with an astronomical price tag that is completely unaffordable? Along the same lines, what good is it to be able to purchase an insurance plan, if insurers are legally allowed to carve out (exclude) vital coverage for your cystic fibrosis/diabetes/cancer? These 3 protections were designed to WORK TOGETHER to protect the most vulnerable in our society. I'm deeply concerned about the current political banter regarding pre-existing conditions because it usually sounds something like this...<br />
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"We want to keep the pre-existing part." </div>
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Most of the time, this one-liner is in reference to protection #1--the legal right to purchase a plan. This is precisely the scenario where we can't let our needs get boiled down to simply having the ability to buy a policy. We also need that policy to be affordable, and to cover the actual treatment of that pre-existing condition in question. It is important that both consumers and lawmakers understand what is at stake here. <a href="https://www.healthcare.gov/coverage/pre-existing-conditions/">https://www.healthcare.gov/coverage/pre-existing-conditions/</a><br />
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I've heard some discussion about the use of "high-risk pools," as a method of insuring those with pre-existing conditions after the repeal of the ACA. This is a strategy that has been utilized in the past (before the ACA), and was a costly disaster for people with cystic fibrosis. If you think premiums are high now...wait until you are dependent on the high-risk pool rates--they are the highest of all!!! High risk patients means high priced premiums--so high that they were completely out of range for many who needed it most. I would encourage those who experienced coverage under a "high-risk pool plan" prior to the ACA to leave a comment. Past experience with this strategy has proven that reducing coverage options to high-risk pools for those with pre-existing conditions was NOT AFFORDABLE, ADEQUATE, or ACCESSIBLE. The failure to provide good healthcare under high-risk pool plans was one of the very reasons why the pre-existing protections were included in the ACA. We absolutely don't want to go backward with our rights to access better coverage plans at lower rates than those offered to high-risk pools.<br />
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<b><u>Ability to Remain on Parent's Insurance until age 26</u></b></div>
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This is much more straight forward than the pre-existing and benefits caps issues. The Affordable Care Act requires insurers to allow children to remain on a parent's plan during the years they are most likely to be still enrolled in college, or have reduced opportunities to obtain insurance through an employer. Prior to the ACA, the cutoff age was 19, or 22 for those enrolled full-time in college. For those with CF, this extension has been shown to be extremely beneficial to continuity and quality of coverage. Please refer to the fact sheet in the link below for further details on this provision.</div>
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<a href="https://www.whitehouse.gov/sites/default/files/rss_viewer/fact_sheet_young_adults_may10.pdf">https://www.whitehouse.gov/sites/default/files/rss_viewer/fact_sheet_young_adults_may10.pdf</a></div>
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<b><u>Medicaid Eligibility</u></b></div>
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1/2 of children and 1/3 of adults with cystic fibrosis depend on Medicaid. The Affordable Care Act expanded Medicaid eligibility requirements--extending coverage to many who were previously not qualified. This eligibility expansion is one of the many provisions of Obamacare on the chopping block with the planned repeal of the ACA. Because Medicaid is utilized by such a large percentage of those with CF, it doesn't take a huge leap in logic to understand that reducing eligibilty would negatively impact the CF community. Those who qualify for Medicaid through the ACA's expanded criteria could face losing that coverage with repeal of this provision. This CF Foundation blog breaks down the details of the Medicaid expansion for those with CF. </div>
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<a href="https://www.cff.org/Living-with-CF/Navigating-Insurance/Medicaid/Medicaid-Eligibility-Requirements/">https://www.cff.org/Living-with-CF/Navigating-Insurance/Medicaid/Medicaid-Eligibility-Requirements/</a></div>
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<b><u>TAKE ACTION</u></b></div>
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If you or someone you love is living with cystic fibrosis or ANY OTHER CHRONIC DISEASE REQUIRING TREATMENT, I hope that you are convinced beyond a shadow of a doubt that changes to healthcare policy will have a personal impact. RIGHT NOW it is a critical time to be a part of healthcare policy discussions, and make our lawmakers aware of how these coverage issues will impact the CF community. PLEASE PLEASE PLEASE follow this link to <a href="http://act.cff.org/ccfpeUx">tell Congress to protect your coverage.</a> You don't need to be a policy expert...the most powerful thing we can do is share personal experiences on why coverage is so vital for those with CF. We need your voice to ensure that healthcare policy changes don't become a painful "sucker punch" to our beloved community.<br />
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***For the record, I understand that high insurance premiums are a concern for many American families whether cystic fibrosis is part of the picture or not. I am not saying that this is not an important issue... but it is a FACT that rising premiums were an issue long before the ACA. I understand that the cost of premiums is prohibitive for many, and we aren't giving up on advocating for lower cost coverage!! The issues I've outlined in this blog, rather, represent the portions of the ACA that would be the most catastrophic for those with CF if repealed (which we anticipate early this year) without appropriate replacement.<br />
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Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com4tag:blogger.com,1999:blog-7535774120903384819.post-77092308660836938082016-10-31T17:30:00.002-07:002016-10-31T17:42:55.904-07:00Exposures and the Human Response--Partnerships for Sustaining Daily Care<div class="MsoNormal">
From my experience, the NACFC has always been saturated with
heavy science…which is fantastic, and has helped create what many may call the
most incredible story of progress in medicine today. I attended my very first Conference in 2011
to see the science for myself, and hell would have to freeze over to keep me
away at this point. In my 6 years
attending this event, I’ve watched the CF research environment EXPLODE. There
are 50+ clinical trials that will take place in the coming year, and more
companies are entering the ring of CF drug development than ever before. The NACFC is attended primarily by the
research community and our clinical care teams, which left me feeling a bit out
place occasionally attending as a CF Mom…so I faked it, and acted like I
belonged. After all, my educational background is in Chemistry, so I wasn’t a
fish completely out of water. This year
though, I felt a shift. The theme of “patient centered care,” and “patient
driven research” came up again and again. I was completely thrilled to see 2
adult patients with CF, and the Mother of twins with CF participate live in a
Plenary session and have the opportunity to address a room of 4500+
professionals who dedicate their careers to CF care and research. In every way,
shape, and form—the patient voice has arrived front and center. Acknowledgement of community participation in
research and care is deeply appreciated. It has been my opinion that we, as the
CF community, have the most to lose or gain—and that our voices should not only
be a valued part of the discussion, but are VITAL to moving forward if we want
research and care to reflect the needs and desires of the patients and families
living with this disease.<o:p></o:p></div>
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This year at the NACFC, I had the opportunity to discuss a collaborative
project that I’ve been a part of for the last 3 years —Partnerships for
Sustaining Daily Care (PSDC). Actually, we originally began as a part of a
Strategic Planning Initiative by the CFF, which brought together several
committees to address the direction of the Foundation’s resources and programs
moving forward. Amazing things, such as the CF Adult and Family Advisors (AFA) have resulted from these
thoughtful efforts. I participated in the strategic planning process as a member
of the committee addressing adherence. Basically, the CFF could see from
Registry and patient reported data, that consistently completing the care regimen
was an issue for many. There is also plenty of research that shows better
health outcomes associated with successfully completing treatment regimens, and
the Foundation saw this as an area where improvements in health and well-being
might be gained WITHOUT a new drug—but by helping patients and families utilize
what we already have at our fingertips. <o:p></o:p></div>
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One thing is for sure—incorporating CF care into daily life
can be extremely difficult. There are numerous challenges that arise: coverage
or access issues to even OBTAIN the medication, time (there are only so many
hours in the day!), or mental health issues like depression or anxiety that can
make completing the care regimen exponentially more difficult—just to name a
few. <o:p></o:p></div>
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<b>FACT</b>: Completing the CF care regimen day after day is
difficult.<o:p></o:p></div>
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<b>FACT</b>: Regular successful completion of the CF care plan results in BETTER HEALTH OUTCOMES.</div>
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<b>FACT</b>: Engaging and empowering patients to give input about their personal goals, and work closely with their care teams to "co-create" the care plan, results in a regimen that is more likely to be sustained. Once we walk out those clinic doors--it is all up to us to balance CF care with our actual lives. I completely understand that there are certain standards of care that our clinic teams must ethically follow, but there is also a tremendous amount of flexibility and creativity that can be employed to also allow patients the opportunity to participate in life in the ways that are most meaningful to them. After all, what is the point of it all, if we miss out on the moments that make life WORTH living?</div>
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For me, discussing some of these challenges with Brady’s
care team has also been difficult. Let me be clear, I absolutely LOVE Brady’s clinical
care team. They have cared for him since birth, and I consider them family!
Brady’s care team is comprised of people that I admire MOST in the entire
world. Even with the great relationship I share with them, being open and
honest about challenges with the care regimen can be difficult because: </div>
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1) For me (type A personality), admitting to my care team that I was having issues with the care plan felt like admitting that I'm not perfect...and that was tough.</div>
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2) Not everyone shares a wonderful relationship with their care team, and discussions around "adherence" to the regimen can take on a judgmental tone. "Why weren't you able to complete every dose of Pulmozyme last week?" can feel more like "What's the matter with you?" The tone and intention behind the communication is extremely important because... </div>
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3) We are sensitive about these issues. Even when we miss doses or treatments, we may still be bending over backward to incorporate CF treatments into our lives. We may have to sacrifice time with our friends, and sometimes have to say no to invitations because it just doesn't work with our CF care that day. There can be some bitterness about missing out on LIFE to care for CF. Also, because of the progressive nature of the disease, we sometimes don't succeed at reaching our goals--even when we do every single goddamn thing right. I know that as a parent, I often took it very personally if Brady didn't meet his weight or lung function goals. It made me feel like a FAILURE.<o:p></o:p></div>
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4) Clinic visits are so long and jam packed already, that bringing up a tough topic like a struggle with depression or anxiety might be the LAST thing you want to do. I know that toward the end of a long clinic visit...I would probably say or do anything just to escape, and get the hell out of there! I may not feel like bringing up my anxiety or depression at that point. These discussions can't take place as an afterthought, because that means they may not happen at all. </div>
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5) Mental health issues, though they are getting talked about more and more, still carry a certain taboo in our society. </div>
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As someone who has personally struggled with anxiety and depression related to CF, I think it is time to move beyond these taboos, and bring mental health out into the open, as a part of our regular clinical care. Last year, mental health was addressed in a big way, as the topic of a Plenary Session entitled: <a href="https://www.cff.org/CF-Community-Blog/Posts/2015/There-Is-No-Health-Without-Mental-Health/">There is no Health without Mental Health</a>. I encourage everyone to follow the link and read more about that amazing session.</div>
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FACT: People living with a chronic disease and those that care for them are more likely to suffer from anxiety or depression </div>
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If you've lived with a chronic disease, or cared for someone who has, these statistics may not come as a surprise. Anxiety and/or depression are absolutely normal human responses to stress and trauma, which are something we are regularly exposed to dealing with CF. For me, it felt like there were sort of 3 main categories: 1) chronic stress, 2) acute stress, and 3) traumatic stress</div>
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Chronic Stress: The daily burden of care can absolutely be exhausting and stressful. Also, when a shortened life expectancy is attached to the disease, worry about long term survival and quality of life are things that can keep us awake at night. I remember when Brady was an infant, it felt like these constant worries were assaulting my brain like a machine gun. It just wouldn't stop. </div>
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Acute Stress: There are so many acute stressors in CF, that I don't even know where to start: pulmonary exacerbations, holding a screaming child down for a procedure/blood draw/throat swab, clinic visits or hospitalizations, explaining CF to someone new, missing something important to you because of CF, the fear of exposure that can come with flu season...the list could go on and on.</div>
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Traumatic Stress: Unfortunately, living with CF can also mean exposure to traumatic stress: a massive lung bleed or lung collapse, undergoing transplant, or losing someone you care about to CF can have a major impact on mental health. </div>
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<b>Exposures and the "Normal" Human Response</b></div>
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We honestly wouldn't be human if these stressors and traumas didn't impact us...and there needn't be any judgement attached to that fact. Let's consider a couple of scenarios.</div>
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1) Your friend was seated next to someone coughing and sneezing their head off with a viral infection on a long international flight. Each cough or sneeze exposes your friend to germs, and a few days after she returns home, she becomes ill. Do you think she is <b><i>weak</i></b> because her body succombed to the same virus? No. Of course not. That seems ludacris.This is a normal human response. </div>
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2) A child exposed to high levels of carcinogens in their environment develops cancer as a result. Do you blame the child for not being able to <b><i>handle</i></b> the pollution?... Not unless you're an asshole! This is absurd. The child's cells began dividing out of control because that is a normal human response to high levels of carcinogen exposure. </div>
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3) A person living with a cystic fibrosis is exposed to the constant stress of the daily management of the disease, and then suffers from a massive hemoptysis resulting in a long hospitalization and time away from family, friends, and the other important things in their life. They become depressed. Do you see that person as incapable because they are struggling? A resounding NO. This is a normal human response.</div>
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4) A Mother worries constantly about the long term health and quality of life for her child because of a cystic fibrosis diagnosis. She finds support by connecting with others in the CF community, and becomes very close to other Moms in the same boat. The support helps her manage daily stress, but she suffers a major surge of anxiety when she learns that someone in her circle of support just lost their child unexpectedly due to a complication of CF. She just can't shake the fear that something similar might happen to her own child. Do you judge this Mom as weak, or incapable? Would you recommend that she just "buck up" and shake it off? I hope it is easy to see the pattern developing here. Anxiety, in this situation, is a completely normal human response. </div>
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When I first began working on the PSDC project 3 years ago, I think I sort of assumed that feelings of anxiety and depression came as a package deal with the CF diagnosis. As a part of the strategic planning process that led to this program, our group poured through literature on how depression and anxiety in chronic illness, and particularly CF. Even though we intuitively understand that mental health is linked to our overall well-being, it made a huge impact on me personally to see data on how mental health was directly linked to lung funtion, and other measures of physical health that we attach great importance to. Similarly, I learned that the mental well-being of the care provider was linked to the physical health of the one being cared for. </div>
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I learned that MY MENTAL HEALTH was linked to BRADY'S LUNG FUNCTION. </div>
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That fact was like a slap in the face to me. I think it is pretty common for caregivers to neglect their own needs, and just give and give to their child or the person they are caring for. Along the same lines, I can imagine that if you are one living with the chronic illness, there are so many physical manifestations of the disease to deal with, that the invisible mental health issues tend to move further and further down the list of priorities. This is why mental health screening and treatment in CF is important. This is one of the important reasons why we need "Partnerships for Sustaining Daily Care." It honestly wouldn't have even occured to me to bring up my own feelings of anxiety and depression in one of my son's clinic appointments, because that didn't seem like the appropriate place and I didn't think that there was anything that could be done about it anyway. In hindsight, it is easy to see that Brady's ability to successfully complete his treatment regimen as an infant and small child was entirely dependent upon my husband and I. If we suffer...he suffers. That was a big AHA moment for me, moving mental health into the "zone of legimate concerns" portion of my brain. </div>
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As the PSDC project takes shape, our hope is to create a cultural upgrade to our clinical care that incorporates mental health into part of the landscape of a routine visit, and create an environment where we feel that we can be safe and honest discussing ANY challenges that stand in the way of completing our daily care. This isn't going to happen overnight, as this is new territory for both patients AND providers. The PSDC group decided that the best way to see these changes take place is to try and understand they we are all human, with similar goals and desires. We participated in several "empathy experiments" to help the care team understand more fully how hard it is to live with CF day in and day out. I also gained a huge amount of respect for how difficult it is for the care teams to do their jobs as well. They also face challenges and frustrations that interfere with the delivery of the best care. We learned to look at one another as people, rather than simply patient and provider. This is about bringing humanity and empathy into our care, and that goes both ways. If anything I've said in this blog resonates with you, the PSDC group would like to hear from you! As we begin creating the ripple for this cultural shift, we want to learn from you. What does partnership with your care team mean to you? Can you think of any instances where you felt like you worked really collaboratively and creatively with your care team to acheive something great? Tell us about it. Can you recall a time when you felt like communication with the care team completely missed the mark? We want to know about that too. Please send your comments to PSDCteam@cff.org.</div>
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I also invite you to join the <a href="https://www.cff.org/About-Us/CF-Community-Opportunities/CF-Adult-and-Family-Advisors/">Adult CF and Family Advisors.</a> Sign up and share your input! </div>
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I had the opportunity to chat about the PSDC in an interactive Facebook Live session at the NACFC this year and you can check it out here! You'll also learn about other cool initiatives the CFF is developing to help connect our community. You can find that interview here: </div>
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<a href="https://www.facebook.com/cysticfibrosisfoundation/videos/10154731243262112/">https://www.facebook.com/cysticfibrosisfoundation/videos/10154731243262112/</a></div>
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If you are having issues with access to medications as a challenge to sustaining your daily care regimen, contact CFF Compass Program for help. compass@cff.org</div>
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Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com3tag:blogger.com,1999:blog-7535774120903384819.post-5080974915580367142016-10-29T15:04:00.000-07:002016-10-29T15:04:17.103-07:00Slides from Plenary 2--Clinical Research:A Worldwide CF Community EffortDr. Michael Boyle wrote a fantastic <a href="https://www.cff.org/CF-Community-Blog/Posts/2016/An-Inspirational-Message-on-the-Worldwide-CF-Community-Effort-to-Advance-CF-Therapies/">narrative of the second Plenary session</a>. Check out the corresponding slides below! My favorite part of this session was the live involvement of 2 adults living with CF, and the Mother of twins with CF! Bringing the patient voice front and center at a research focused Conference is truly groundbreaking! Enjoy!<br />
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Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com6tag:blogger.com,1999:blog-7535774120903384819.post-17153016585445446712016-10-29T14:30:00.000-07:002016-10-29T14:30:11.158-07:00Genome Editing Potential for Cystic FibrosisPeople always ask what new information from NACFC excites me the most. I've listed my top 3 below, and will go into further detail about one of those--Gene Editing, as the topic of this entry.<div>
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<b><u>Rebecca's Top 3 from the NACFC</u></b></div>
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<b>1) The sheer number of new correctors and potentiators appearing in clinical research </b>has exploded! There are almost too many of them to even keep track...and they are certainly NOT all coming from Vertex. There is a robust pipeline and a competetive surge to get these compounds on the market.</div>
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2) <b>The development of new ways to measure CFTR function and personalized drug response.</b> Small "organoids" can be grown from rectal tissue biopsy, nasal brushings (nasopheres), or bronchial tissue (bronchospheres). Once harvested, these cells can allow researchers to test whether or not an individual might respond to a drug treatment. As the number of new CFTR modulators increases, and as we try to treat patients with rare mutations, these techniques could prove to be extremely valuable. Once the cells are harvested, they can be reproduced indefinitely outside of the body, and drugs can be tested on a person's organoids in the lab as a good predictor of a clinical response in that individual. This kind of testing could streamline early phase clinical trials, and provide the safety of testing drugs in the lab vs. in vivo. <div class="separator" style="clear: both; text-align: center;">
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3) <b>Gene therapy strategies as a potential CURE for ANY mutation of cystic fibrosis.</b> Investigators are examining several different techniques, as seen in the slide below. This entry will focus on CFTR gene editing using the CRISPR/Cas9 system.</div>
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<span style="background-color: white; color: #363636; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.85px;">One method of gene editing utilizes a system call CRISPR Cas9. </span><b style="background-color: white; color: #363636; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.85px;">CRISPR</b><span style="background-color: white; color: #363636; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.85px;"> stands for </span><b style="background-color: white; color: #252525; font-family: sans-serif; font-size: 14px; line-height: 22.4px;">clustered regularly interspaced short palindromic repeats--</b><span style="background-color: white; color: #252525; font-family: sans-serif; font-size: 14px; line-height: 22.4px;">specific targets on a gene, containing short repetitions of base sequences, followed by short segments of "spacer" DNA. <b>Cas9</b> is a single DNA targeting enzyme that serves to "code" for proteins related to CRISPRS. In simpler terms, the CRISPR can be thought of as the specific portion of DNA targeted for alteration (the section where we find the presence of the CF mutation). Cas9 can be thought of as a tiny pair of scissors, programmed to make a cut in the strand of DNA at precisely the right spot. This is a complicated process, but is explained nicely in this video produced by the CFF and shown during the first Plenary Session. </span></div>
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Dr. Hao Yin from the Massachusetts Institute of Technology in Cambridge, MA gave a talk on Thursday afternoon entitled: </div>
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<b><i>In Vivo Genome Editing: From Proof-of-Concept to Therapeutic Delivery.</i></b> </div>
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Dr Yin's study utilized mice with a hereditary liver disease (tyrosinemia type I)</div>
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caused by a genetic mutation. He was able to demonstrate that CRISPR cas9 mediated correction of a genetic mutation in live mammals was truly possible, and has the potential for correction of human genetic diseases like CF. As seen in the video, gene editing is a complex process. In this study, Dr. Yin combined lipid (fat) nanoparticle mediated delivery of Cas9 mRNA (messenger RNA) with adeno-associated viruses, and a repair template to induce gene repair in living mice. He was able to show that the mice exhibited short-term expression of the Cas9 nuclease by in vivo mRNA delivery, which provided efficienct on-target genome editing, and reduced off-target editing (altering the genome at unintended sites can obviously be problematic!). </div>
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This proof-of-concept study is extremely exciting, but several challenges still remain. Two primary issues that investigators have always struggled with in regard to gene therapy strategies are the precision and specificity of targeting, and the method of delivery inside the nucleus of cells.</div>
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One method of getting information through the cell membrane to the inside of the cell is to use a modified virus to sort of "infect" cells with new information. </div>
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It is profound that investigators have shown gene editing techniques may be successfully performed in living mammals, but there is still considerable progress to be made before we see these therapies in humans. At last year's NACFC, I also shared my excitement about development of these <a href="http://luckycfmom.blogspot.com/2014/10/beyond-small-molecules-gene-editing.html">new gene therapy techniques</a>. I'm really optimistic that progress will continue to accelerate in the coming year, and more exciting trials will be reported in 2017! </div>
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Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com4tag:blogger.com,1999:blog-7535774120903384819.post-81080510723947684282016-10-27T23:44:00.003-07:002016-10-27T23:47:32.421-07:00Slides from the first Plenary Session of NACFC 2016. A Cure for All:Leaving No One BehindThe CFF has already produced a wonderful blog that detailing the <a href="https://www.cff.org/CF-Community-Blog/Posts/2016/On-the-Road-to-a-Cure-Pushing-for-Treatments-for-Everyone-With-CF/">first Plenary session</a>. Thank you Katherine Tuggle! Here are the slides that correspond with her narrative. Enjoy <3<br />
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<br />Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com3tag:blogger.com,1999:blog-7535774120903384819.post-74844579079600897182016-10-27T23:28:00.000-07:002016-10-27T23:28:05.718-07:00NACFC2016--Notes from Day 1<div class="MsoNormal">
This is my 6<sup>th</sup> year attending the NACFC, and I
always consider it the absolute most exciting 3 days of the my entire
year. We spent most of yesterday traveling
from northern Idaho to Orlando, and celebrated our arrival by connecting with
old friends over cocktails. <o:p></o:p></div>
<div class="MsoNormal">
The workshop sessions kicked off this morning. I ran as fast
as I could (in heels with a bad knee!) between rooms to catch the talks that
had piqued my interest most, but spent most of my time in—<o:p></o:p></div>
<div class="MsoNormal">
<b><u><br /></u></b></div>
<div class="MsoNormal">
<b><u>Clinical Advances in
Cystic Fibrosis Research</u><o:p></o:p></b></div>
<div class="MsoNormal">
<i><b>Comparison of Lung Clearance Index and Magnetic Resonance
Imaging for Assessment of Lung Disease in Infants and Preschool Children with
CF.</b></i></div>
<div class="MsoNormal">
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjvkfmk84ATEccYWupKsVDfIe6OA21Hqli_ga9MhFHeg5cT28HZedLGoZ8a3E9L9e1YCVsoGTqRe-9KMVRFT_PiS6Rhwp2hymorzqqDlT8yKsJiix58Fp8BlLME3vAUIreXqG8zV4KCVB4/s1600/20161027_094839.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjvkfmk84ATEccYWupKsVDfIe6OA21Hqli_ga9MhFHeg5cT28HZedLGoZ8a3E9L9e1YCVsoGTqRe-9KMVRFT_PiS6Rhwp2hymorzqqDlT8yKsJiix58Fp8BlLME3vAUIreXqG8zV4KCVB4/s640/20161027_094839.jpg" width="640" /></a></div>
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There are a couple of important points that I hope to drive home from this discussion. </div>
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<span style="text-indent: -0.25in;">1)There is a robust body of data showing that lung
disease begins early in life in children with CF—often in the first few weeks
or months, and that this early progression in the smallest airways often takes
place in the complete absence of symptoms.</span></div>
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<span style="text-indent: -0.25in;">2) There is a need for a highly sensitive, non-invasive
method to examine early structural lung changes. Currently, we don't have a reliable standardized technique to measure lung function for children too young to properly perform spirometry.</span></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEizfGbq2DE00qbUipXTE-NkQ8EVmo-wpzXsoYy7_QaysMyrwS16lbHZqbaW20_1lPVwmRbksEkBxHTlc_MGhp6tvQtxj7ncrueWbRnX1PeRlxfbeNY692t2677gFCY4gJGvV8daUc-tolU/s1600/20161027_094931.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEizfGbq2DE00qbUipXTE-NkQ8EVmo-wpzXsoYy7_QaysMyrwS16lbHZqbaW20_1lPVwmRbksEkBxHTlc_MGhp6tvQtxj7ncrueWbRnX1PeRlxfbeNY692t2677gFCY4gJGvV8daUc-tolU/s640/20161027_094931.jpg" width="640" /></a></div>
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This study examined the relationship between a measurement
called Lung Clearance Index (LCI), with structural lung changes determined by
MRI. Determining LCI in children <4 requires sedation and
administration of a “tracer gas,” and takes between 30-60 minutes to
perform. </div>
<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjsGIEFLEjlReegpU2nCzVFBDfioG3YKlTB463dULsG48kLbkMD0rU87Ofhd82_EbIgH6UQsVgkNZqgTvGXOIOOibTuJnTmOCx7zPRkqcVGrhXGAjQUmY7uLz5UMBfLbL3qnGNB6_LngYU/s1600/20161027_095131.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjsGIEFLEjlReegpU2nCzVFBDfioG3YKlTB463dULsG48kLbkMD0rU87Ofhd82_EbIgH6UQsVgkNZqgTvGXOIOOibTuJnTmOCx7zPRkqcVGrhXGAjQUmY7uLz5UMBfLbL3qnGNB6_LngYU/s640/20161027_095131.jpg" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">*MBW stands for "Multiple Breath Washout." </td></tr>
</tbody></table>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgoVQBR5UlyL4XZcUjW1IYGLPx5-l4fu2tMJp_MMR3UfdwOjqIR930tySYE7h1yMaHJy6aLwUvzxGWI9qbLKjvNwaU7l98y8xz8C5F-dsFM65KRKAFitJtxiA6ryorwJYHzhOBKHLPCTxE/s1600/20161027_095241.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgoVQBR5UlyL4XZcUjW1IYGLPx5-l4fu2tMJp_MMR3UfdwOjqIR930tySYE7h1yMaHJy6aLwUvzxGWI9qbLKjvNwaU7l98y8xz8C5F-dsFM65KRKAFitJtxiA6ryorwJYHzhOBKHLPCTxE/s640/20161027_095241.jpg" width="640" /></a></div>
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Dr. Mall’s data showed a
correlation between LCI and structural abnormalities on MRI. He suggests that
LCI may be an effective tool for monitoring early lung disease progression, and may offer opportunities for early intervention. He also suggests that LCI may be a
reasonable endpoint when conducting clinical trials. </div>
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To be honest, this discussion wasn't the most exciting talk on my schedule today. LCI is a technique that I've learned about in previous years, but hasn't arrived in clinical practice as a standard of care. The data on early progression of lung disease in the absence of symptoms is not new information either (<a href="http://luckycfmom.blogspot.com/2012/03/cf-lung-disease-does-symptomless-safe.html">AREST CF study</a>). I think it is important to understand that structural changes in the lungs begin very early in CF--"in the first few weeks or months of life" and can be measured. Also notable is that these changes in the very smallest airways can occur in the complete absence of respiratory symptoms. By the time an individual has become symptomatic, damage has already occured. Cystic fibrosis progresses silently in our youngest patients, and finding ways to measure those changes might offer potential opportunities for intervention. Furthermore, as we discover more new therapies to treat CF, it is essential that we have reliable methods to test their effectiveness in our youngest patients. </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhsiPDD2bvpKeXvmxlTh5cmm9LMXTCMyIDdlcUzSOSjPfJdNJlGW_D1KcFBKIi1oYBhl_j5AcL947hwbPrFQpFfGM5w07yAubnTzgLJ2opAQqUpOxsN9dztN5wLjV49mhEaEEt38h1wV5I/s1600/20161027_095902.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhsiPDD2bvpKeXvmxlTh5cmm9LMXTCMyIDdlcUzSOSjPfJdNJlGW_D1KcFBKIi1oYBhl_j5AcL947hwbPrFQpFfGM5w07yAubnTzgLJ2opAQqUpOxsN9dztN5wLjV49mhEaEEt38h1wV5I/s640/20161027_095902.jpg" width="640" /></a></div>
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<i><b>My opinion</b></i> is that preserving structural lung health in pediatric patients <i>with or without symptoms </i>is extremely important, and finding a way to accurately measure the progression of disease in these youngest patients will allow researchers to ultimately find better ways to treat and PREVENT structural lung damage with early intervention strategies. </div>
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Next up:</div>
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<i><b>Long-Term Safety and Efficacy of Ivacaftor in Pediatric
Patients Aged 2-5 Years with CF and a CFTR Gating Mutation.</b></i><o:p></o:p></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhiaXdyKu9_qjr2JbepYLviX_A0vwo_jYnDYF6NElv7PFQR8p1v007839T2GX_dWsX2FpXuOEhw7sO4p9l3s8qeWyILsWrL64T3K3czYbGGYxN2pi913-2h8EuArFSM0y-xFRMNzFmZEG0/s1600/20161027_100408.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhiaXdyKu9_qjr2JbepYLviX_A0vwo_jYnDYF6NElv7PFQR8p1v007839T2GX_dWsX2FpXuOEhw7sO4p9l3s8qeWyILsWrL64T3K3czYbGGYxN2pi913-2h8EuArFSM0y-xFRMNzFmZEG0/s640/20161027_100408.jpg" width="640" /></a></div>
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Ok…It felt like this talk was being given directly to ME.
For the record, my son Brady began treatment with Kalydeco almost immediately after it was approved
in January 2012. The drug was initially approved for children 6+, and Brady was
only 4 at the time. We (my husband, I, and Brady’s care team) decided it was in
Brady’s best interest to start taking the drug immediately, to halt the cycle of
disease progression and PREVENT as much lung damage as possible. We fought for
coverage, and were able to start treatment on Feb. 10<sup>th</sup>, 2012. Brady
has been taking Kalydeco for over 4 1/2 years, and during that time, the FDA extended the approved usage to children as young as 2. We know that we have seen huge benefits in Brady's health, but it was really nice to see some data on usage in this age group. </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjESblXLTYLQj_J7nbwrA0XmUXa_ts_jBqMQuFaZ91uyflhRFvpDiC68RoxTcWARdzIwElwYubgbY_qqXxZsWX8qRU_7NKZKs696_nX40alyYNMuQjRVGyuwR0EErCCxTlbrT1u6zjY5VI/s1600/20161027_100456.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjESblXLTYLQj_J7nbwrA0XmUXa_ts_jBqMQuFaZ91uyflhRFvpDiC68RoxTcWARdzIwElwYubgbY_qqXxZsWX8qRU_7NKZKs696_nX40alyYNMuQjRVGyuwR0EErCCxTlbrT1u6zjY5VI/s640/20161027_100456.jpg" width="640" /></a></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEihcoZ1Xe3JMZ3cisaflTPmh3Js-_ivFtTg0RkA-tYdXGPMfj-pvxgmlu1R2HDLhoGUAkix9hLKCmLwmqjgp9eBouOa9z_NCvbFmrI38VBkHqR4_mxVJMpSs4tDohLYjXh_Bv0H-a0gu1s/s1600/20161027_100614.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEihcoZ1Xe3JMZ3cisaflTPmh3Js-_ivFtTg0RkA-tYdXGPMfj-pvxgmlu1R2HDLhoGUAkix9hLKCmLwmqjgp9eBouOa9z_NCvbFmrI38VBkHqR4_mxVJMpSs4tDohLYjXh_Bv0H-a0gu1s/s640/20161027_100614.jpg" width="640" /></a></div>
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The KLIMB study followed children taking Kalydeco though 84 weeks of treatment.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhQnKdtf8gnUs2cS5G4ZQLO7g5cpqDLPCs2QTFMpkq34Qc68Jf7gpe8pZAGzt1_M9575H0vGJoVPk4oln5dzzJvcIPM_aNPY1u7KNcQL6syNBu27mgdmiYO-od2_OtreWAEjNDMRpfFgFw/s1600/20161027_100714.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhQnKdtf8gnUs2cS5G4ZQLO7g5cpqDLPCs2QTFMpkq34Qc68Jf7gpe8pZAGzt1_M9575H0vGJoVPk4oln5dzzJvcIPM_aNPY1u7KNcQL6syNBu27mgdmiYO-od2_OtreWAEjNDMRpfFgFw/s640/20161027_100714.jpg" width="640" /></a></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhsq_jvZmlJ8n2A4SKueJ4lOhdCguyBz2S_GN1Z5-Ttm_Ej8JSvCIKIgs6J4sA5HRuy-RHV6YBlk2rOpqZpx0oDeN9Nr7gXkTaNhT5Oh0pwXh2qDeDhaZS6dc1ouy2hNiLJsT39vkwNCUI/s1600/20161027_101019.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhsq_jvZmlJ8n2A4SKueJ4lOhdCguyBz2S_GN1Z5-Ttm_Ej8JSvCIKIgs6J4sA5HRuy-RHV6YBlk2rOpqZpx0oDeN9Nr7gXkTaNhT5Oh0pwXh2qDeDhaZS6dc1ouy2hNiLJsT39vkwNCUI/s640/20161027_101019.jpg" width="640" /></a></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg8hxO4TuYSahAnWfA5-mZa9zLKoX5dHEk927uWy6HfY3ohI7fzeVr_rtVG2Niu3QsBDEYJhrnFQoVfTpzrVXeEcZ4PFVKYJwxR0STUVPxHV-7L2OQWF5Patz_N7T_eoJueHV6ZglZ7YAw/s1600/20161027_101119.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg8hxO4TuYSahAnWfA5-mZa9zLKoX5dHEk927uWy6HfY3ohI7fzeVr_rtVG2Niu3QsBDEYJhrnFQoVfTpzrVXeEcZ4PFVKYJwxR0STUVPxHV-7L2OQWF5Patz_N7T_eoJueHV6ZglZ7YAw/s640/20161027_101119.jpg" width="640" /></a></div>
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Data from the KLIMB study showed that the benefits seen immediately after initiation of Ivacaftor treatment were statistically sustained through the 84 week extenstion period. Changes in fecal elastase (a measure of pancreatic function) were also observed in some of the youngest patients, indicating potential for improved or some restored pancreatic function.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjNDXheIYEuSH_xZURabmjV9hjkyeKIvI6Z0PtCYRJtZ2UrE-sWIrhoOyIKLdRbFLfU9f8XXhfHmr6hkmmE4t-5SqmW2eg3U4x6JKYnzun-xNl_BfALn3kFPAwXuCX8_Z0PXjvqOj-oTk0/s1600/20161027_101203.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjNDXheIYEuSH_xZURabmjV9hjkyeKIvI6Z0PtCYRJtZ2UrE-sWIrhoOyIKLdRbFLfU9f8XXhfHmr6hkmmE4t-5SqmW2eg3U4x6JKYnzun-xNl_BfALn3kFPAwXuCX8_Z0PXjvqOj-oTk0/s640/20161027_101203.jpg" width="640" /></a></div>
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The changes in fecal elastase (first reported in the KIWI study) came as a surprise--as restoring any pancreatic function for CF patients was previouly thought to be impossible... Additionally, no new safety concerns were reported.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjKrZrmw2EOAMtj42P9SMNCAhVHexwAI_9i35ojxq2ezb_eh8-dyeDoXwzi0o1Cxe6b_vjdIc9hX5tE6ASSsNNcO603t75lmNAD53WiKhms8fXmZ4hApHOIuZwqi6aF-5rpiokFldpttlk/s1600/20161027_101440.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjKrZrmw2EOAMtj42P9SMNCAhVHexwAI_9i35ojxq2ezb_eh8-dyeDoXwzi0o1Cxe6b_vjdIc9hX5tE6ASSsNNcO603t75lmNAD53WiKhms8fXmZ4hApHOIuZwqi6aF-5rpiokFldpttlk/s640/20161027_101440.jpg" width="640" /></a></div>
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It is exciting to imagine what we might be able to achieve as CFTR modulators reach younger and younger patients. Personally, I am reassured beyond doubt that we made the right decision by fighting for early access to Kalydeco. According to CFF President and CEO Dr. Preston Campbell--initiating a CFTR modulator like Kalydeco early in life may REMOVE the traditional life expectancy limits associated with CF and allow individuals to thrive into their '70s and '80s. I truly believe that the length and quality of Brady's life will not be regulated exclusively by cystic fibrosis. When I see the data like this I wonder what types of changes we might be able to see if we started in newborns? Could there be a future where we are even able to treat a fetus with CF in utero??</div>
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The last talk I'll summarize in this entry was entitled:</div>
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<b><i>Relations between Potentiator response in Organoids in vivo. Outcome Parameters in Patients with CFTR Gating Mutations.</i></b></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi3Wjh7rCBzeIM-f37aeHGQVPZ-7KHfMcZmL_RB8ieN6NV_qvTCnEzpoEiYp7zSlZ_dJOf52_g941ft1s38i_xvBbYZ-XcCFxz1hvPA1EdZHp5L-Z5nFaI4VVuS4_hloe_Xe1taeFRZED0/s1600/20161027_102021.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi3Wjh7rCBzeIM-f37aeHGQVPZ-7KHfMcZmL_RB8ieN6NV_qvTCnEzpoEiYp7zSlZ_dJOf52_g941ft1s38i_xvBbYZ-XcCFxz1hvPA1EdZHp5L-Z5nFaI4VVuS4_hloe_Xe1taeFRZED0/s640/20161027_102021.jpg" width="640" /></a></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi05b5vET6191AM2hYNA3WQv1WhhaxKMcPDOhuOJAyZ3rrfPLj0ItGKBbxp0-uqaA412yX59caus0cshzLjscrPtiDfLyI4pqXDdOYZWM9dHscw8n_YbWyE0wrzjncBCTLztI9BrSxD5iw/s1600/20161027_102117.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi05b5vET6191AM2hYNA3WQv1WhhaxKMcPDOhuOJAyZ3rrfPLj0ItGKBbxp0-uqaA412yX59caus0cshzLjscrPtiDfLyI4pqXDdOYZWM9dHscw8n_YbWyE0wrzjncBCTLztI9BrSxD5iw/s640/20161027_102117.jpg" width="640" /></a></div>
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One theme that I heard woven through many of today's discussions was the desperate need to develop novel methods of determining which patients will respond to which CF modulator therapies. Organoids can be thought of as "mini organs." These organoids live in our digestive tract and can be harvested by rectal biopsy. </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh35cPnD_UH5X_JiBLNAmuCMKFZdP5FESsx_yf3koC8Htg_nE3HkMOkykQ0ZLTd8azKzMxNOSsC9Sra3tVj_eTt2eCRhUqGWstFkHLVKIhgjyIyEXsXRd_sTri-VXF9cLY5BggBO49I2eQ/s1600/20161027_102203.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh35cPnD_UH5X_JiBLNAmuCMKFZdP5FESsx_yf3koC8Htg_nE3HkMOkykQ0ZLTd8azKzMxNOSsC9Sra3tVj_eTt2eCRhUqGWstFkHLVKIhgjyIyEXsXRd_sTri-VXF9cLY5BggBO49I2eQ/s640/20161027_102203.jpg" width="640" /></a></div>
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Organoid swelling is correlated with CFTR function (much better correlation than CFTR function with sweat chloride levels, for example). This enables researchers to test drugs on organoids and predict whether people with specific mutations will respond to a particular compound. </div>
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<tr><td class="tr-caption" style="text-align: center;">The organoids on the left show normal swelling associated with functional CFTR. The middle panel shows diminished swelling in F508del homozygotes. The organoids on the right exhibit the increase in CFTR function when F508del homozygotes were treated with Orkambi.</td></tr>
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<tr><td class="tr-caption" style="text-align: center;">For the purposes of this study, organoids with the S1251N mutation were utilized.</td></tr>
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Finding new ways to measure CFTR function is extremely important if we want to achieve our mission of reaching 100% of patients with a CFTR modulator therapy. Many mutations of CF are extremely rare, and this technique is being used to help researchers determine if those individuals might respond to existing therapies like Kalydeco or Orkambi. In the future, organoids could allow scientists to test which combination of correctors and potentiators will have the most profound effect on that individual's CFTR function (because we will have multiple potentiators and correctors to choose from in the future), and mixing that cocktail can be tricky business! Another advantage of this technique is that once the tissue biopsy is obtained, endless organoids can be obtained or "grown" from this initial sample for subsequent study--"biobanked." </div>
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My work in advocacy has taught me the importance of developing new ways to accurately test CFTR function and drug response. The goal is to be able to treat every individual with CF with small molecules (potentiators, correctors, and various combos of both). The discovery of which drugs work for which mutations is a first step. Furthermore, to obtain FDA approval and vital insurance coverage, there is a need for some cold hard DATA. My opinion is that organoid studies will enable researchers to streamline early drug discovery for rare mutations, and also support evolution of the FDA's drug approval process. Organoid studies may not sound very glamorous, but developing endpoints that accurately correlate with CFTR function is a crucial step in helping new drugs reach the individuals that will benefit. </div>
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This entry represents just a few of the talks I attended earlier today. Lots more to come tomorrow! </div>
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<o:p></o:p>Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com8tag:blogger.com,1999:blog-7535774120903384819.post-950062825047964312015-10-15T13:19:00.000-07:002015-10-16T07:53:37.558-07:00The Personalizing Research ProjectI had a sort of epiphany on the trip home from the NACFC . After 5 years as a "normal person" attending this Conference (the vast majority of attendees are: research scientists from academia, biopharma peeps, clinical care team members, investors, and a hundred or so major donors to the CFF), I have built a number of important connections with <b>scientists</b> working on understanding and testing the CFTR protein, or manipulating the gene somehow to correct for mutations.<br />
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<b style="font-size: x-large;">My Concerns</b><br />
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Currently, the biopharmaceutical industry is holding the reins as the driving force in drug development and innovation for CF. Of course, the Cystic Fibrosis Foundation carefully selects which projects to invest in, and does an excellent job of promoting competition to drive prices down...eventually. This is, in no way, a critique of the actions of the CFF. I hope that everyone that reads my blog understands my position on the actions of the Cystic Fibrosis Foundation. You might even say I am a "superfan." I have participated in the Strategic Planning Committee for the Foundation, served on the Patient Engagement Advisory Council, worked as the volunteer chair of the Great Strides walk in Spokane for the last 2 years, attended the CFF sponsored NACFC Conference for the last 5 years, and had their "Adding Tomorrows" logo tattooed on my body. As much as I love what the CFF is doing, they don't possess the power to control big pharma. <br />
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Also, for the record--there is NO DOUBT that partnering with biopharma has resulted in some huge innovations in the treatment of CF. Note that my only other tattoo is that beautiful Kalydeco molecule on my left foot, reminding me everyday to "Honor the Gift" we have been given with this Vertex developed miracle.<br />
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My observation is that we (patients/families) cannot rely on big pharma to put patients before investors, and the CF Foundation has limited power over things such as cost of any successes resulting from their investments (as we have seen painfully with Kalydeco and Orkambi). I see a number of issues brewing, that could potentially slow down our progress toward better combinations of potentiators and correctors. Because I know first hand how life-changing these drugs can be...I think that sucks. I want to do more than line the pockets of executives and investors...we have the power to enhance the lives of patients and get important people considering the patient as a real part of this equation<i>. </i><br />
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<b>The FDA and Randomized Placebo Trials</b><br />
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Before I launch into this, I want to say that the FDA has been an amazing partner in CF progress. The passage of the <a href="https://www.cff.org/About-Us/Media-Center/Press-Releases/Statement-from-the-Cystic-Fibrosis-Foundation-on-Passage-of-the-EXPERRT-Act-in-House-of-Representatives/">EXPERRT Act</a> in 2012 gave the agency the flexibility it needed to even consider some of the specialized therapies we are bringing their way. With consideration to Kalydeco and Orkambi, the FDA provided swift, expert review--bringing the drugs to patient hands in the safest, most expedited manner. When considering expansion of the Kalydeo label to include the R117h mutation, the FDA listened carefully to patient testimonials, and made the <i>right </i>choice to expand access to these patients in the end. The FDA has been extremely helpful to us, and has shown that it has the potential and desire to evolve. Right now, we are entering some really murky territory with the FDA. Traditionally, the FDA has required data from large scale, randomized, placebo controlled trials as a means to gain approval for marketing a drug in the U.S. How would you feel about the following situation? I would sincerely appreciate anyone who would take the time to leave a comment with their thoughts.<br />
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<i>Your child has a residual function mutation, and is benefiting from Kalydeco. A better potentiator is discovered, but enrolling in the clinical trial for this compound would mean a 1/3 possibility of receiving a placebo for up to 20 weeks. Would you take the chance of going off Kalydeco, and enroll in the trial anyway?</i></div>
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<i>You are an adult with advanced lung disease who has been taking Orkambi for several months. The initial few weeks were tough, but you are seeing some benefits, as well as some side effects. Other companies are racing toward clinical trials with alternatives to Orkambi that present with better in vitro CFTR activation, and potentially safer toxicology report. A few months ago, a hiccup in insurance coverage caused you to miss several days of Orkambi suddenly, and resulted in a serious (and scary) exacerbation. If you have the chance of getting assigned a placebo, and going back to non-functional CFTR for a portion of this trial...do you enroll?</i></div>
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<i>You are heterozygous, and want to ensure that the most effective potentiators, correctors, and transcriptional read-through agents get approved to treat your specific combination of CF mutaions, but Vertex has the CF community locked down with their combo for heterozygotes--which is furthest along in development, and will reach the market first. If the majority of eligible patients are accessing this first option that gets to market, who are we going to test better combos on?</i></div>
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Let me stress again that this is not a direct attack on Vertex--they are simply acting like a business. Vertex just happens to be out in the lead of this race to treat/cure CF, and they are playing the game like any other for-profit pharmaceutical company would. Also imporant to note is that I view the research scientists at Vertex in a much different light than I see the executive leadership. I have completely mixed emotions--reverence mixed with disgust for Vertex--and the situation is anything but black and white. What I am suggesting, rather, is for enriched patient dialog with the FDA, as we may need to change some rules to see our progress take place in a way that encourages innovation. I want to make sure that the patient is at the center of the business of curing CF, rather than Vertex alone calling the shots. As I mentioned before, I would appreciate your comments on these important issues. </div>
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In a discussion I attended at the NACFC, I had a bit of a battle with an FDA reviewer. Please take a look through the slides of his presentation, and consider what is at stake here. I think this is important to be aware of for everyone with CF--whether you are currently taking a CFTR modifier or not. </div>
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<tr><td class="tr-caption" style="text-align: center;">This slide clearly mentions the ethical concerns I have been discussing, but the FDA reviewer seemed to play it off as relatively minor. He did NOT believe that asking patients to come off of Kalydeco or Orkambi to test potentially superior combos would be a formidable problem to trial enrollment...What do you think?</td></tr>
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Dr. Durmowicz was asked a question in regard to the ethics of using placebo controlled trials for upcoming CFTR modulators, and pulling patients off of treatments like Kalydeco or Orkambi, that that may exhibit clearly positive benefits, to test potentially better drug combinations. </div>
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Dr. Durmowicz casually remarked that patients wouldn't mind doing it...in the name of progress. <b> *This is where I begin feeling extremely agitated.</b> In my experience with Brady missing doses of Kalydeco due to a stomach bug, and accounts that I have heard from others within the CF community--the "rebound effect" can produce some seriously unpleasant side effects, and in worse cases--potentially dangerous exacerbations. Not to mention the MENTAL sabotage of finally feeling a dream come true in finally being able to breathe with greater ease, and then being asked to go back to a disease+ state of being. In my opinion, that is So. Not. Cool. <br />
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I worry that the best case scenario is that the trials experience significant delays in enrollment. Worse case scenario is that drugs that could have a meaningful effect can't enroll at all, and the projects can't move forward! Additionally, I think that FDA regulators are underestimating how hard it can be to come off of CFTR modulators. I have seen and heard from many patients that withdrawal from CFTR modulators can induce an exacerbation, and may produce much less meaningful trial data. As soon as FDA reviewer Dr. Durmowicz made the remark...steam started pouring out of my ears. I didn't want to do it, but I couldn't help myself. Something gripped me, and I felt myself rise, and walk to the mic. I had no choice. I introduced myself as a CF mom with a child taking Kalydeco and explained that I "respectfully disagreed" with his opinion before I gave him a mouthful. I assured him that no one wants progress more than we do, but our mutual goal is going to be extremely hard to achieve if we can't get patients to enroll in trials they might consider to be unsafe and/or unethical by design. My comments to the FDA regulator drew applause from the audience, and several drug manufacturers approached me afterward to cheer my efforts, and remark that they have the same concerns. The owner of one company in particular, who is developing an alternative drug for homozygous patients, expressed great excitement over his discovery--but worried about the ability to move forward against a "Vertex monopoly." As a chemist, I fully understand the need to test these drugs with scientific rigor, to ensure a safe and effective product for the patient consumer...but I also think we are entering uncharted territory with personalizing drugs to alter an individual's cellular biology. If the FDA's main concern is SAFETY, I propose that cycling patients off and on CFTR modulators might have some very unsafe consequences and produce less than meaningful data. We have a responsibility to at least try to minimize the collateral damage as we continue on this very personalized journey to the perfect CFTR modulator cocktail for each patient. Please share YOUR EXPERIENCES transitioning on and off CFTR modulators in the comments. I feel like I have heard a lot of anecdotal remarks, but I am increasingly curious to get a greater body of feedback on this issue. If the FDA doesn't understand our concerns--the responsibility rests on our shoulders to educate them. <br />
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In our current environment, we would be naive to rely on for-profit pharmaceutical companies to have our best interests at heart. The same is true for Vertex that is true for other virtually any other pharmaceutical company--the investor is their #1 priority. As much as I love what companies like Vertex have been able to accomplish in drug development--I am absolutely NOT OK with the $$$ amount placed on my child's health every month. The astronomical price of their innovations has led many countries to be delayed or denied access of Kalydeco and Orkambi. I am NOT OK when families in several countries around the globe write to me in desperation because their loved ones are being denied access to Kalydeco or Orkambi. Watching someone you love deteriorate before your eyes with CF is torture...watching them deteriorate, knowing there is an existing drug that could alter their lives if you could only access it is a special kind of bitter pill that I wouldn't ask anyone to swallow. There have been access issues here in the U.S. as well, with one woman in Arkansas waiting over 2 years before getting coverage for Kalydeco. Many CF patients rely on Medicaid or State programs that have limited budgets, and these are some of the most expensive drugs ever marketed... This situation sickens me because I know precisely how life changing CFTR modulators can be for some patients--patients like my son Brady. I want to see MORE CF patients benefiting from these drugs RIGHT NOW, and NEW DRUGS come to market to effectively treat MORE PATIENTS in the future. <br />
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<span style="font-size: large;"><b>What Can I Do?</b></span><br />
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<b>1) Leave a comment for me to share with the CF Foundation, and the FDA. </b><br />
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<b>*This blog represents my views alone as a CF Mom, and while I do serve as a volunteer, I am not speaking or writing on behalf of the CFF. I will, however, be sharing feedback on this issue with them, because I feel they are an important ally for the patient population.</b><br />
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<b>2) Subscribe to the PRP--The Personalize Research Project</b><br />
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At the same time we are helping regulatory guidelines evolve, I've discovered another powerful technique where I feel that the patient community might be able to make significant influence. In my experiences at the NACFC over the last 5 years, the interactions I've had with scientists have been extremely powerful, and in some cases--altered the course of research. For me, this year's NACFC was a perfect storm of advocacy, science, emotion, connection, influence, and empowerment. In the grand scheme of using my specific talents to make the greatest impact in advancing our community toward the cure--I have finally crystallized my focus, my calling, and my goal--to not only personalize the delivery of clinical care for CF patients, and to advocate for a system that meets the needs of patients--but to take it even one step further--and<b style="font-style: italic;"> </b>advocate for<b> <i>personalizing</i></b><b><i> the research</i></b> as well. When I say personalize, it means two things:<br />
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1) <b>Personalize research techniques</b> to effectively test and combine compounds to give the greatest benefit to each individual patient.<br />
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<li>Encourage use of techniques utilizing human airway cells, organoids, nasal epithelia, and animal models developed with specific mutations to obtain the richest data to predict in-vivo clinical correlations. </li>
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<li>Encourage the use of n-of-1 trial design to allow those with rare mutations or combinations to benefit from CFTR modulator therapies.</li>
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2) Personalize the research by making it about the patient. Personalizing as in, <b>making it personal</b>. <br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhMY2dKbaYHMXLepYfNcA7MCmRyWlfNGEouqCmTsqkNzEB0K68_e78tWkv6puScDT3w_-VP-nfQ_7GC80HwMOTRXUBEl1BZZoh-7m5XItsZcqhHPKmaOTC5yDj22QsW_Iq9YuJAZNjg7gE/s1600/_MG_6227+%25281%2529.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="320" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhMY2dKbaYHMXLepYfNcA7MCmRyWlfNGEouqCmTsqkNzEB0K68_e78tWkv6puScDT3w_-VP-nfQ_7GC80HwMOTRXUBEl1BZZoh-7m5XItsZcqhHPKmaOTC5yDj22QsW_Iq9YuJAZNjg7gE/s320/_MG_6227+%25281%2529.jpg" width="256" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Ultimately, the work done in the lab has an enormous effect on real people...like Brady.</td></tr>
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For me, coming face-to-face with research scientists gives me the opportunity to enhance their understanding about why individualizing care options is so important. I do everything I can in these interactions to make them actually care a little bit about Brady. I want them to think about Brady while they are at work in the lab everyday. I want them to understand that their work is so incredibly important, and that we appreciate the hell out of it. I want to influence the person actually holding the test tube, and/or developing the new scientific techniques we will use to cure CF. Even industry drug developers got their start in a University lab somewhere, I want them to understand what it means to live with CF. Allowing these scientists to understand our struggle in a little more personal way injects their research endeavor with infinitely more <b style="font-style: italic;">meaning </b>(beyond just publishing a paper, or getting another graduate student through their program). I want to bring the patient/family voice directly to the lab bench. We DO belong at the table along with academia and industry. I think this is desperately important in the current drug development environment.<br />
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<b>Making the Connection</b><br />
I get a similar reaction every time I put myself face to face with a research scientist. First of all, they are surprised that I am there, and that I am so knowledgeable about CF science. I always thank them for making their career about CFTR science, and do my best to convey the details of how deeply chemistry and the understanding of the CFTR protein has impacted Brady and our family. Many of them are moved to tears, and write to me later that our meeting was the most meaningful part of the Conference for them, and they ask permission to share the story with their grad students and department. <br />
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<b>The Ripple</b><br />
CF will eventually be cured in a lab somewhere, and I want whoever is behind that cure to care about CF patients a little bit (preferably a lot!)--or at the very least feel some sort of ethical awareness of how their work is impacting actual patients living with this awful disease. Scientists represent the SOURCE of our progress with understanding and treating CF. I believe that personalizing the lab work (with the presence of the CF patient/family voice) could serve to <i>infinitely</i> magnify the size of the ripple we are able to make in the research arena.<br />
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<b><span style="font-size: large;">The Evidence</span></b><br />
I have witnessed or been a part of these real instances where a patient or parent interacting with a researcher has had a powerful influence. For privacy, I have left the names and specifics out of the following scenarios, but these represent REAL EVENTS that I have witnessed at NACFC. Please share comments if you have experienced the power of the patient/scientist connection. <br />
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<b>Case #1</b>) CF Mom who is searching for data on the action of her daughter's rare mutation gets seated next to an important research scientist at dinner. By the end of the night, the scientist realizes he has a cell line in the freezer with the daughter's mutation from a former study he had conducted, and agrees to pull it out and perform a few experiments to see whether Kalydeco might offer some benefit. The tests show potential for benefit and Mom is able to build a case to obtain off-label coverage. Mom obtains first script of Kalydeco and is able to document benefits. Patient has now been able to benefit from Kalydeco for several years before she would have otherwise, and the entire research lab now has a personal connection to CF. <br />
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<b>Case #2</b>) CF Mom gets seated next to important research scientist at dinner. She discusses her son's rare mutation, and her efforts to obtain more knowledge about the potential for current therapies to impact the mutation. Research scientists invites Mom and her son to visit their lab and donate some cells for them to run tests on. Mom gets more information about her son's mutation, and the entire lab team now understands the implications of their work as they move forward with their experiments.<br />
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<b>Case #3</b>) I attended the NACFC for the first time in 2011 and saw the phase 3 trial data for VX-770. I was also able to get face-to-face with investigators familiar with the preliminary data on VX-770 in younger kids. As a result, I understood that future expansion to younger children was undeniably on the horizon--more a matter of time to meet regulatory requirements, than concerns over safety in this younger group. Armed with data, I was able to build a case for off-label coverage of Kalydeco, and access the drug more than 2 years before it is "approved" for my child's age group. <b>*I am not claiming, by any stretch of the imagination, that attending the NACFC guarantees off-label coverage of anything. Coverage happens on a case by case basis. I am saying, rather, that detailed knowledge of both the mechanism of action of VX-770, paired with data regarding testing in children guided me to at least TRY to access this drug for my child. I am saying that if I hadn't attended the NACFC, Brady would have waited 2 more years before starting Kalydeco. Personally, I wouldn't dream of missing the NACFC, because the knowledge I've gained there has had a significant impact on the real life consequences of the disease for my son. Period. </b><br />
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I want to clarify that I am not claiming that interactions with scientists are more important that interactions with the care team. More accurately, the clinical care team tends to have a better understanding of what CF means, and typically have many "personal" connections to patients and families living with CF, due to their regular interactions in clinic and the hospital. Research scientist often have absolutely zero connection with patients or understand how hard it can be to live with CF. I see interacting with scientists as a sphere of opportunity where we are currently absent, where we have the power to exert a large amount of influence. <br />
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<span style="font-size: large;"><b>So What.</b></span><br />
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In regard to the goal of <b><i>personalizing research</i></b> to offer the most benefits and the least risks <b><i>to every individual</i></b>--I encourage you to <b>leave comments</b> on this blog as well as <b><a href="http://nu.salsalabs.com/o/50674/p/salsa/web/common/public/signup?signup_page_KEY=6843">sign up as an advocate</a></b> on the CF Foundation's website. I have no doubt that issues will arise demanding action from advocates as we move forward. The CF Foundation has amazing policy experts, and they allow us to organize our efforts and make the biggest impact. Every year I come home from the NACFC with deeper insight. I have witnessed so many important ways that the patient voice is missing, or misunderstood. I think that at this point in history, it is extremely important that we continue to advocate for a system and regulations that support our goals.<br />
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We can't afford to stop communicating. The FDA is evolving right along with medicine, and the CF Foundation has truly developed an exemplary relationship with them over the years. When I go to meetings on Capitol Hill requesting increases in FDA funding--I tell the story of how swiftly and expertly the FDA reviewed the Kalydeco application, and how much that meant to my family. I want the FDA to be able to do the same for every drug we send their way, and they need proper resources to do it! In my experience in working with the FDA, the patient voice seems to be deeply regarded, and is a powerful tool (as we saw with the impact of patient testimonials in the expansion of Kalydeco to the R117H mutation). Many on the voting committee remarked that hearing from the patients themselves made a huge impact on the way they voted. We need to continue working and communicating deeply with the FDA, as the complexity of our research endeavors demand. I think there is an enormous potential to work together here, and show the world how curing disease is done!<br />
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I will be be exploring some of the techniques available today to test individualized therapies in a future blog. Researchers see potential in testing on human organoids, nasal epithelial cells,and animal models with specific mutation combinations to bring greater precision to testing, and minimize risks to patients.<br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiOJXO48of-jH8WlpL3s4D05wd30Ulqlllxw9d0RxBa_kuU4fxGQeuYyozBejsTPDeOsMzQybicurI4pHY2S0NJc1G3LojHxs2B2tx7P-7oSB2CdWWB4yyUanbpSFM9hz1FXheeUELONtE/s1600/organoid.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiOJXO48of-jH8WlpL3s4D05wd30Ulqlllxw9d0RxBa_kuU4fxGQeuYyozBejsTPDeOsMzQybicurI4pHY2S0NJc1G3LojHxs2B2tx7P-7oSB2CdWWB4yyUanbpSFM9hz1FXheeUELONtE/s400/organoid.jpg" width="380" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Organoid studies provide an exciting opportunity to test the effect of drug combinations on individual patients. </td></tr>
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Lastly, I want to share a dream of mine, that I would like to see materialize--Each time I get the opportunity to connect with a CF scientist, I think to myself--"Man, it would be so awesome to be able to visit their lab, and get to have a conversation with everyone who works there." If someone were to ask me about my "dream vacation," it would be akin to a world CFTR laboratory tour--so I think I should do just that. If the goal is to personalize research for CF, getting face-to-face with the person holding the test tube is a good way to start. I know I need to start talking about this dream, to promote some general awareness, which will hopefully lead me to my next step--financing. In the meantime, I will be following up with every scientist I had the pleasure of visiting with at the NACFC, and exploring invitations I've already received. It is time to blow the top off of the idea that patients don't have a place at the research bench. For truly personalized medicine in a disease community with over 2000 disease causing mutations, I argue that patient voices are the missing "secret sauce" that will help usher in the cure we have all been dreaming of, while simultaneously acting to limit the power of big pharma. *Drop Mic*<br />
<b>**IMPORTANT NOTE. This blog is NOT in any way advising against the infection control guidelines outlined by The Cystic Fibrosis Foundation. They are based on the latest science, and are there for a reason--safety. I attended the NACFC Conference as a parent, and believe that meaningful connections can also be made using technology to connect patients with researchers.</b>Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com5tag:blogger.com,1999:blog-7535774120903384819.post-44636826522242889642015-10-09T17:39:00.000-07:002015-10-09T17:39:59.012-07:00Understanding the link between CFTR and Insulin Function--NACFC 2015<div class="separator" style="clear: both; text-align: center;">
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Back to business. Time for one quick summary before I head to a special dinner. <br />
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<b><i>Impact of CFTR on Beta cell
Function in the Pancreas--presented by Dr. Antoinette Moran. </i></b></div>
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I found this talk really interesting
and hopeful. Development of cystic
fibrosis related diabetes is extremely common, and the risk increases with
age. CFRD places an additional large
treatment burden on patients, and is associated with a number of negative
health outcomes.<o:p></o:p></div>
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Abnormal insulin secretion has been shown to begin very
early in life—even in children with normal oral glucose tolerance tests. </div>
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This early abnormality led the researcher to
question whether the abnormality was present at birth (an intrinsic defect), or
developed over time (acquired defect). Studies
using the CF ferret model show that the animals are born with abnormalities—suggesting
that this is an issue present at birth. <!--[if gte vml 1]><v:shape id="Picture_x0020_4"
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With this knowledge in hand, Dr. Moran was curious to
examine the link between CFTR function and insulin secretion. The link between exocrine function of the
pancreas (the release of digestive enzymes) and the presence of functional CFTR
is fairly well understood. The same
basic mechanism of mucous dehydration and mucous plugging that causes scarring
in the lungs, also leads to ductal blockages in the pancreas--thereby impairing
digestive enzyme secretion. The
connection between CFTR and endocrine function (insulin secretion), is still
being uncovered. The question Dr. Moran
posed in this study was whether restoration of CFTR function with a drug like
Kalydeco might be able to improve insulin secretion, and prevent or delay the
onset of CFRD. <!--[if gte vml 1]><v:shape id="Picture_x0020_3" o:spid="_x0000_i1025"
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First, Dr. Moran set out to determine whether CFTR was, in
fact, present in the insulin secreting beta cells in the pancreas. Evidence is not 100% conclusive, but highly suggests that CFTR is in fact present in these cells. </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgWuvu2YXrrB2HsnZrkDXeGtFj4Pdj7GviA3m5-HdeUuWjg0ppu45uqdyp8jZN4M9xvT9wfo8xq8UILiLjBdZP3lRh7JoOzXW02nGE9JjlrfktU-GDE8VMAW9kHjXUCXdGMwlTFejxvK0k/s1600/20151008_153718.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgWuvu2YXrrB2HsnZrkDXeGtFj4Pdj7GviA3m5-HdeUuWjg0ppu45uqdyp8jZN4M9xvT9wfo8xq8UILiLjBdZP3lRh7JoOzXW02nGE9JjlrfktU-GDE8VMAW9kHjXUCXdGMwlTFejxvK0k/s640/20151008_153718.jpg" width="640" /></a></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgiI5zBTnBmvp3pn_b8kczeTz22wG7lGP2W_qRRTbedcNOphkP3QkO8foAwesmbw5zMADHfl9eiGqeIpnhhTWxOzDuCsRfeE9YYV-q9bb69wkKPrdMRLqFH6dshHytsPBlbPjAlmxU5uNw/s1600/20151008_153826.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgiI5zBTnBmvp3pn_b8kczeTz22wG7lGP2W_qRRTbedcNOphkP3QkO8foAwesmbw5zMADHfl9eiGqeIpnhhTWxOzDuCsRfeE9YYV-q9bb69wkKPrdMRLqFH6dshHytsPBlbPjAlmxU5uNw/s640/20151008_153826.jpg" width="640" /></a></div>
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The role of chloride transport (by way of CFTR), has never been included in the classic model of insulin secretion. </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEin3IT3eFICLW4C8E40acRciiH7NtngN-cDu2HNOcomPkGrnM9CAQKcPOiZIyPfk6RPiFcO5zfXcpMc4URfuOkLpiAhtsBl52m8UXQiGNqc9BdzHXx47lkjV1Ri7cWAW1tecqVa8AZvZc8/s1600/20151008_153925.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEin3IT3eFICLW4C8E40acRciiH7NtngN-cDu2HNOcomPkGrnM9CAQKcPOiZIyPfk6RPiFcO5zfXcpMc4URfuOkLpiAhtsBl52m8UXQiGNqc9BdzHXx47lkjV1Ri7cWAW1tecqVa8AZvZc8/s640/20151008_153925.jpg" width="640" /></a></div>
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Dr. Moran believes that there is sufficient evidence to update this model to include the role of the chloride channel.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgcWUhjpkcnAuXkPp2ibOBvdmxmP-B_xI5PtNquiyx4WDrMCFs1tD4j6qx0MVapPsSA4xcHe586DFuyQEaHv0Bv04yDxLdluqN9a8eQLxB1us5jIJaXjLO63gpF7lHDWcNJK78KHVqXnQI/s1600/20151008_154229.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgcWUhjpkcnAuXkPp2ibOBvdmxmP-B_xI5PtNquiyx4WDrMCFs1tD4j6qx0MVapPsSA4xcHe586DFuyQEaHv0Bv04yDxLdluqN9a8eQLxB1us5jIJaXjLO63gpF7lHDWcNJK78KHVqXnQI/s640/20151008_154229.jpg" width="640" /></a></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgRmpaM14JFdxfTRtv0qimBc5EXq1VE4STIZVyeXnIT6ndcuiPd65Zenbhe7xmf_G8rb4EUM4nYznXAZXc9IC7yYPRtnWDcXzU1JKsrlfzLcm7W6vO_1ygXt1hMtSNgLVsHKQ8enP6rh4A/s1600/20151008_154051.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgRmpaM14JFdxfTRtv0qimBc5EXq1VE4STIZVyeXnIT6ndcuiPd65Zenbhe7xmf_G8rb4EUM4nYznXAZXc9IC7yYPRtnWDcXzU1JKsrlfzLcm7W6vO_1ygXt1hMtSNgLVsHKQ8enP6rh4A/s640/20151008_154051.jpg" width="640" /></a></div>
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Ultimately, this study examined the insulin secretion of a small group of patients before, and after one month of therapy with Ivacaftor.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg6Q6SX5qVZ9JiJkI-3SyCKlNj1yBNQ7bghyphenhyphenmeLrCpx_tFxdgvON0U-i4QXAc7e_Z2GWFGFUTWAJWuduWUvtdBfjBcre598YDrlgCIliSrVdNgaXxtyMicRVcU8d5YNP4eKkrrkE91Q9mg/s1600/20151008_154517.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg6Q6SX5qVZ9JiJkI-3SyCKlNj1yBNQ7bghyphenhyphenmeLrCpx_tFxdgvON0U-i4QXAc7e_Z2GWFGFUTWAJWuduWUvtdBfjBcre598YDrlgCIliSrVdNgaXxtyMicRVcU8d5YNP4eKkrrkE91Q9mg/s640/20151008_154517.jpg" width="640" /></a></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgZ_TBy1qU7nqS06fFo1FLRMh1g1ddJmzV8RRZdY-1XItdNZ6iSxXfWpe5OA4K0l2rDlgteCqj_ZT4HFHXNpWa6FpRub9G4d4hp9N9UoNE6MzSVoDfpIQ1s_gdbkgFqL-Zk3yt_CVEdQnA/s1600/20151008_154439.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgZ_TBy1qU7nqS06fFo1FLRMh1g1ddJmzV8RRZdY-1XItdNZ6iSxXfWpe5OA4K0l2rDlgteCqj_ZT4HFHXNpWa6FpRub9G4d4hp9N9UoNE6MzSVoDfpIQ1s_gdbkgFqL-Zk3yt_CVEdQnA/s640/20151008_154439.jpg" width="640" /></a></div>
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As shown in the bar graph, treatment with Ivacaftor produced a significant improvement in insulin secretion. This is "tantalizing evidence" that correction of CFTR with a modulator drug like Kalydeco has the potential to delay or prevent the onset of CFRD. Dr. Moran noted that while Type II Diabetes develops differently than CFRD, there may be potential to augment insulin secretion for this group as well with amplification of CFTR function. <br />
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While there is certainly more work to be done in this area of study, I walked out of the room with the hope that Kalydeco may help prevent CFRD for my son Brady and many others. <br />
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<o:p></o:p>Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com1tag:blogger.com,1999:blog-7535774120903384819.post-6944566334813952972015-10-09T02:50:00.001-07:002015-10-09T07:48:06.923-07:00NACFC 2015--Details from Day 1<div class="MsoNormal">
This morning, the action began at 10 a.m. with a host of
workshops. Because there are always
multiple interesting talks happening at the same time, Brock and I decided to
divide and conquer to take in the most information. Here are the most interesting nuggets from my morning.<o:p></o:p><br />
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I was anxious to hear the results of the European Gene
Therapy Trials at the NACFC <b><i>last</i></b> year, but the UK team backed out last minute in order to
complete their data collection process.
I was able to see their data earlier this year in a videotaped
presentation by Dr. Alton, but this was the first time that the trial results
have really been shared at a meeting like this, with the professional CF community at large. <o:p></o:p></div>
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<i><b>A Randomized, Double-blind, Placebo-controlled Trial of
Repeated Nebulization of Non-viral CFTR Gene Therapy in Patients with Cystic
Fibrosis. Presented by Dr. Eric Alton<o:p></o:p></b></i></div>
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While research in the U.S. has been focused on the “small
molecule” approach to treating CF, scientists in the UK have poured a
tremendous amount of time and energy into gene therapy.
The UK CF Gene Consortium has been working for years on this project,
and has encountered considerable obstacles along the way. The most formidable challenge has been
identification of an effective vector to transmit genes inside the lung cells
of CF patients. Many viral vectors were
tested and abandoned due to the high inflammatory response they elicited (infection by virus
is one way to breach the cell wall and gain access to the DNA held inside, but
was found to cause too much collateral inflammatory damage to be an effective
candidate). Ultimately, a lipid (fat)
vector was chosen to perform a phase 2b placebo controlled trial in
humans. Trial participants were asked to nebulize a gene therapy solution once a month (approximately 40 minutes to complete treatment). Ultimately, the study showed statistically significant improvements in FEV1. </div>
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Patients exhibiting the most severe lung disease showed the least benefit from this treatment, and Dr. Alton hypothesizes that fibrosis and mucous barriers associated with more severe lung disease could be obstructing the interaction with lung tissue--preventing the transfer of the healthy gene. <br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgQxw5QNoB-ClHO25v5fin_4cecgCZLyD45fFRAsEMvoXeY1U7RnSOC_yr0EvOvQNMuBWoo8T_mOQpXLiafOQckR8mKDGuLVlTQrYgd60XOuaqXSrqALSfJw6tH8sO4_8qS2Hcyvr5HWgo/s1600/20151008_104840.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgQxw5QNoB-ClHO25v5fin_4cecgCZLyD45fFRAsEMvoXeY1U7RnSOC_yr0EvOvQNMuBWoo8T_mOQpXLiafOQckR8mKDGuLVlTQrYgd60XOuaqXSrqALSfJw6tH8sO4_8qS2Hcyvr5HWgo/s640/20151008_104840.jpg" width="640" /></a></div>
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Dr. Alton believes that this study, while modest in benefit, provides proof of concept that gene therapy should be further developed as a tool for treating CF. The next steps would involve pushing the boundaries to see if further benefit might be obtained with higher dosages. Also, if gene therapy is able to activate a small amount of CFTR in the lungs, there is the possibility that the chloride transport by this small amount of CFTR could be enhanced with the addition of a small molecule potentiator such as Kalydeco. <br />
<br />
While gene therapy is an exciting concept, it is something that researchers have been working on for decades--basically since the discovery of the CF gene in 1989. The treatment benefits seen in the trial were modest, but represent the greatest success to date using this approach. Dr. Alton seems determined to continue down this road, but I have doubts... Personally, I think that the gene-editing or mRNA editing techniques (such as CRISPR-cas9 that we will hear about later in the conference) hold more promise as a way of actually changing an individual's genetic expression. Just my opinion. I was hoping for much better data after so many years of development. <br />
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<b><i>Mesenchymal Stem Cell LL-37 in Cystic Fibrosis. Presented by Tracey Bonfield</i></b></div>
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Human mesenchymal stem cells (hMSCs) come from bone marrow, and are able to differentiate and develop into many different cell types in the body. There is no need to suppress the immune system to utilize hMSCs, making them an attractive candidate for therapy development. </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEizQM_I2WBWDdewV_uVN1t1sZ6xAgBglJKPwxSFa_gODnFkb5kg7nLNplwymfffVntSGbBjHfR3M6xv9U-2Df-4SE09TbXfMPhTO7qtRwH1Q3MN1Qj9efPbsoNJLJusWGMvwS-o04AM_fk/s1600/20151008_105655.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEizQM_I2WBWDdewV_uVN1t1sZ6xAgBglJKPwxSFa_gODnFkb5kg7nLNplwymfffVntSGbBjHfR3M6xv9U-2Df-4SE09TbXfMPhTO7qtRwH1Q3MN1Qj9efPbsoNJLJusWGMvwS-o04AM_fk/s640/20151008_105655.jpg" width="640" /></a></div>
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For this study, the CF mouse model was used to test how hMSCs might affect CF lungs. The mice were infected with Pseudomonas aeruginosa and then treated with hMSCs. The mice were followed for 10 days. The data collected suggests that hMSCs exhibit both anti-inflammatory as well as anti-microbial properties. The rate of Pa growth in the mice was decreased, and combination with an antibiotic treatment produced a synergistic effect (augmented the potency of the antibiotic). </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhGwN3hVqK4QCJ7p4gKUMMQdoiPqY8VeafoeMA2rfnY3ANqvyOkIG9RtyNwpNHJY7P6zsK8FFFM5UCk34yY8OHbdX9ldhAxjpHUpPHSSPwE52pFisoxfDYFzPJw4TrqpB9PgEMZjzRUtjk/s1600/20151008_110535.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhGwN3hVqK4QCJ7p4gKUMMQdoiPqY8VeafoeMA2rfnY3ANqvyOkIG9RtyNwpNHJY7P6zsK8FFFM5UCk34yY8OHbdX9ldhAxjpHUpPHSSPwE52pFisoxfDYFzPJw4TrqpB9PgEMZjzRUtjk/s640/20151008_110535.jpg" width="640" /></a></div>
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While this work is preliminary, this trial in mice shows measurable benefit, and further studies with hMSCs to treat CF lungs will be coming our way in the future.<br />
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<i><b>Hormone Fluctuations Correlate with Respiratory Symptoms in Patients with Cystic Fibrosis. Presented by Raksha Jain.</b></i><br />
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Existing data has suggested that women with CF have worse health outcomes than men. Women demonstrate earlier colonization with respiratory pathogens and an increased exacerbation rate near ovulation. This study examined the role that sex hormones play in CF. <br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEin5lF3r0jmQU7_Ov7nxWRAQSv-pY0h4SCCv6BLBQYw-1iwTfJ5KT48wwrTes7uj0ldYvGll-vSuexhyphenhyphen304RZRvOuauo7n17p5y12D47nUwP_j0344robFDtGAt9ruteWxMb7tQZ3HMM78/s1600/20151008_111118.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEin5lF3r0jmQU7_Ov7nxWRAQSv-pY0h4SCCv6BLBQYw-1iwTfJ5KT48wwrTes7uj0ldYvGll-vSuexhyphenhyphen304RZRvOuauo7n17p5y12D47nUwP_j0344robFDtGAt9ruteWxMb7tQZ3HMM78/s640/20151008_111118.jpg" width="640" /></a></div>
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This was an observational study where hormones were measured throughout the course of the menstrual cycle. Inflammatory markers were measured, and patient reported data was collected as well. Additionally, data was collected for women with CF who were asked to cycle on and off birth control pills--which function as an estrogen inhibitor.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhF__hQ_4OqQF1XeEaLLzFOBvuxTJmR7vKO2BjJVRz1UraBF8YTaEQM-dWRE8aejgVkaiWd1EDJgyDuCoyPEMV9mR7_-oiDPwGBTHCYpkz5dKRoUTkrc3lSec3_hnwGLpGEu7jThGHVV8w/s1600/20151008_111534.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhF__hQ_4OqQF1XeEaLLzFOBvuxTJmR7vKO2BjJVRz1UraBF8YTaEQM-dWRE8aejgVkaiWd1EDJgyDuCoyPEMV9mR7_-oiDPwGBTHCYpkz5dKRoUTkrc3lSec3_hnwGLpGEu7jThGHVV8w/s640/20151008_111534.jpg" width="640" /></a></div>
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The data they collected basically suggests that higher estrogen levels correlate to worse respiratory symptoms. This was shown with an increased rate of exacerbation during the follicular phase of the menstrual cycle (when estrogen is highest). It was also shown that suppression of estrogen with oral contraceptives trends toward reduced exacerbations, and should potentially be examined as a therapeutic option (this was a very small study, so these findings are suggestive rather than conclusive). </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiRKA5u0aCA0d_n24difSOS_IKje-h_3GonjMHvBdh9YzWuPl7geyWcVENKw0jdlM3LKLzMptU9NJmOtEVa17frRvDHhcG7FqISfel4A6TYlVtxR5qVhigSReSpCoXzs8tB_EQgyqlOMLc/s1600/20151008_112228.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="360" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiRKA5u0aCA0d_n24difSOS_IKje-h_3GonjMHvBdh9YzWuPl7geyWcVENKw0jdlM3LKLzMptU9NJmOtEVa17frRvDHhcG7FqISfel4A6TYlVtxR5qVhigSReSpCoXzs8tB_EQgyqlOMLc/s640/20151008_112228.jpg" width="640" /></a></div>
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The take-away message--further study is warranted to determine if oral birth control pills may represent a way to improve the health status of women with CF through the suppression of estrogen. </div>
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These 3 studies represent a tiny fraction of the discussions I saw today (I didn't even make it to my afternoon notes yet--but I have to be able to stay awake tomorrow)! </div>
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After the morning session concluded at NACFC, Brock and I dashed over to the Volunteer Engagement Conference at the Renaissance to snag some lunch and connect with other CF families. I also had the privilege to speak about advocacy alongside Mary Dwight and Abi Green from the CFF, and my CFF National Advocacy co-chair Melissa Shiffman (who filmed an awesome advocacy video that I will be able to share when the link is made available). Nothing inspires me to preach advocacy like spending my morning listening to the amazing scientific progress that is happening RIGHT NOW. </div>
<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhmArDKkYGPOmS5EAWnRhe-V949reoyLxNXwzJUEuO0TPSusdR7EFU_0fEpen59FnRxxeO-LekEiQgvK-3x5NSXRrbw0ftzFGrB-WGhDHfH-ks7xMacAQefqxxclQdCO7yFEsrUofGobks/s1600/speech.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhmArDKkYGPOmS5EAWnRhe-V949reoyLxNXwzJUEuO0TPSusdR7EFU_0fEpen59FnRxxeO-LekEiQgvK-3x5NSXRrbw0ftzFGrB-WGhDHfH-ks7xMacAQefqxxclQdCO7yFEsrUofGobks/s400/speech.jpg" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">I made it on and off stage without falling on my face--success!</td></tr>
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It makes me sick to my stomach to think about struggling with access barriers when we have so many wonderful opportunities speeding through the drug development pipeline. I feel strongly that advocacy needs to be a priority for anyone who cares about the future of someone with CF, because progress means absolutely nothing in the absence of access. I love analogies, and in my mind, we--the CF community-- are all piled in this homespun machine, moving closer and closer to the finish line (curing CF). </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi9drSjtLpxkHqwPvqcA7AuEkCnzullRkAQyk7OfaC-prcktHzdvp3puI0Dzpe0llEehD91qQHIKteoXKsJlOWUhgImnfmzwp5YFk44xonwJNKp31aBNeIRLaxNmdjAjBo4WvApwfwmuyg/s1600/machine.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="225" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi9drSjtLpxkHqwPvqcA7AuEkCnzullRkAQyk7OfaC-prcktHzdvp3puI0Dzpe0llEehD91qQHIKteoXKsJlOWUhgImnfmzwp5YFk44xonwJNKp31aBNeIRLaxNmdjAjBo4WvApwfwmuyg/s400/machine.jpg" width="400" /></a></div>
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Inside our machine are multiple interlocking gears that must mesh and spin simultaneously. The awareness gear interacts with, and helps power fundraising--which leads to scientific investments--which ultimately bring new drugs and therapies into existence. </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg-FtSxSzcnJbyWjXXkL3TExVl2W1ghFUXVfH5Ot3N3I1aPKQnxXV9Tmx1PK3XBxS1FwGDIaYSWY4_Ixp5zAcbQUxzgS3I6ehUsib2jE3sYW-wCwt7mWV-d9CgfmDljkwQooIqeuICFdls/s1600/4-interlocking-gears-clear.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="240" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg-FtSxSzcnJbyWjXXkL3TExVl2W1ghFUXVfH5Ot3N3I1aPKQnxXV9Tmx1PK3XBxS1FwGDIaYSWY4_Ixp5zAcbQUxzgS3I6ehUsib2jE3sYW-wCwt7mWV-d9CgfmDljkwQooIqeuICFdls/s320/4-interlocking-gears-clear.png" width="320" /></a></div>
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The engine of our machine is humming along at breakneck speed! BUT, there is another crucial juncture we must attend to, where all our inner gears interact with the axle (the ADVOCACY gear). This is the gear responsible for physically spinning the wheels to propel us forward. If we fail to make that interaction with our system, our inner gears will be left to simply spin...while our machine goes NOWHERE.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg9cf08nDfnN1iz71hJt-61N7mzhnq_RP-tDGXK84mr47MTXWKCfDkGXDmKisqH6YBVWI9M3SAZyZA1sHy514VZBKJf4fvE14sFop_-3RxpYBvKyEAFudEX2DHJwgRGu-pYcYLoMQjLZow/s1600/crucial.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg9cf08nDfnN1iz71hJt-61N7mzhnq_RP-tDGXK84mr47MTXWKCfDkGXDmKisqH6YBVWI9M3SAZyZA1sHy514VZBKJf4fvE14sFop_-3RxpYBvKyEAFudEX2DHJwgRGu-pYcYLoMQjLZow/s1600/crucial.jpg" /></a></div>
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You can imagine that it wouldn't take very long for those spinning wheels (and impatient families) to build up some intense heat. </div>
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I believe that we MUST advocate to avoid a situation where the inner gears of our machine are held back by a structure that isn't ready/willing/capable to help us move those wheels closer to our goal. Imagine for a second that advocates HADN'T recently been successful at passing the Ensuring Access to Clinical Trials Act (EACT), and we had the money and science to move forward with exciting clinical trials--but barriers to trial participation stood in our way and slowed us down... I know that I would get hot under the collar in a hurry. Knowing the passionately CF community the way that I do, I think we run the risk of some serious engine trouble in that situation. We can't let that happen. </div>
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<tr><td class="tr-caption" style="text-align: center;">Advocate regularly to avoid engine trouble!</td></tr>
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With that, I will close for tonight. Tomorrow is another full day of workshops and symposium sessions. Plus, I need to be at my best for lunch with Dr. Beall, and dinner with some of the best scientists in the world. Stay tuned--we are just getting started!</div>
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Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com3tag:blogger.com,1999:blog-7535774120903384819.post-30820560964289885872015-10-08T09:21:00.000-07:002015-10-08T09:21:28.806-07:00Welcome to NACFC 2015<div class="separator" style="clear: both; text-align: left;">
The North American Cystic Fibrosis Conference brings
together thousands of brilliant scientists and clinicians to discuss their
research, and ways to improve care in CF clinic. As a CF Mom with a
chemistry degree, I am drawn like a magnet. The conference is
draining--physically, intellectually, and emotionally. I subsist mostly
on coffee, wine, and protein bars and don't sleep much. I am a zombie by
the time I get home, and my head spins for weeks on all the new information I
have learned, and people I have met...and I wouldn't miss it for the world!
I even attended in 2012 on crutches after knee surgery. It would
take a natural disaster of some kind to keep me away.</div>
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This year, there is a new event piggybacked on the NACFC
called the “Volunteer Engagement Conference (VEC), which will bring volunteers
from the West together for scientific updates and Foundation news. My husband and I arrived in Phoenix yesterday
afternoon and attended a beautiful welcome reception for volunteers and
Foundation leadership at the home of Robert and Carole Griego. It is always really special to me when I get
the chance to spend time with other CF families. I’m excited to speak at the VEC this
afternoon about the importance of prioritizing advocacy as we move through an
evolving healthcare system toward personalized treatments for cystic
fibrosis. <o:p></o:p></div>
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As you can imagine, there is a mountain of new scientific
information to digest every year. I have every expectation that this year
is going to BLOW MY MIND. This morning, my plan is to attend the workshop
entitled “New Advances in CF Animal Models.”
I’m going to send my husband Brock to the “Novel Targets and Outcome Measures”
workshop to take notes and pictures. I
hope to have another post later today about what we learned. After lunch, I will be speaking at the
Volunteer Engagement Conference alongside Mary Dwight and Abi Green from the
Foundation, and my National Advocacy co-chair Melissa Shiffman.<o:p></o:p></div>
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This afternoon, I will be attending a symposium-- “Partnering
with Patients and Families to Promote Healthy Lifestyles,” which will feature
discussion about exercise, alternative therapies, anxiety management, and
wellness through diet. After that, we
will attend the first Plenary session—“Personalized Medicine,” where several
speakers will discuss the process of tailoring the care and drug regimen to the
needs/mutations of each individual patient.
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It is such an awesome feeling to sit in the huge room where
the Plenary sessions are held--surrounded by 4000+ professionals who all care
deeply about curing CF. It is like being transported to another planet
where, fortunately, I speak the same language as the natives. <o:p></o:p></div>
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I’m a little nervous about my knee brace/high heel combo, so
hopefully I don’t take a nose dive down the escalator! Barring disaster, I will
be blogging to the best of my ability again this year. Stay tuned for updates!<o:p></o:p></div>
Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com1tag:blogger.com,1999:blog-7535774120903384819.post-44509170665153785032015-03-23T10:11:00.000-07:002015-03-23T13:46:29.825-07:00Come to the Table<div class="MsoNormal">
I hate politics. I
really do. I haven't taken a political
science course since Freshman year. All the partisan bickering and lack of action on important issues is annoying and
frustrating. It often seems like
campaigning for the next election is all many of our politicians care about,
and I can’t stand to watch live television during an election cycle because it
makes me want to throw things at my TV…<o:p></o:p></div>
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So why in the world would I travel from northern Idaho to
Washington D.C., suit up, and walk 8 miles in heels navigating the maze of
offices on Capitol Hill? Why do I feel absolutely
compelled to inject myself into that political world and lob my heart onto the
lovely mahogany desks of my elected representatives? Because I am a mother of a child with cystic
fibrosis. For me, this is not
political—this is personal. <o:p></o:p></div>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEitsfBJxqtOUHiEhwGfVdLp166QbtKR2H1YLDMn3RUZG7e8FHduz8kncXQEzpZzzCBH2VM-ovrEOFohzDb0Qv8aspx8bbq4nedIRNYPIFxWNkvcb-Y4WGIbsElOaW9w8NtxzLb_BKmed7I/s1600/superhero_meeting.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEitsfBJxqtOUHiEhwGfVdLp166QbtKR2H1YLDMn3RUZG7e8FHduz8kncXQEzpZzzCBH2VM-ovrEOFohzDb0Qv8aspx8bbq4nedIRNYPIFxWNkvcb-Y4WGIbsElOaW9w8NtxzLb_BKmed7I/s1600/superhero_meeting.jpg" height="241" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Brady is 7 years old, and LEGO obsessed! Sometimes it feels like my whole world looks like this!</td></tr>
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Whether we like it or not, our healthcare system is
evolving, and every year lawmakers are voting on legislation and budgets that
will directly impact families and patients living with cystic fibrosis. The Cystic Fibrosis Foundation understands
this, and has been working to establish a presence on Capitol Hill for many
years. On March 19, over 120 CF advocates, representing 38 states participated in 273 meetings in the CF Foundation’s “March on the Hill”
event. This is an opportunity for CF experts (YOU!)
to come to the table, and educate elected officials on what it means to live
with cystic fibrosis. It is our
opportunity to bring the unique needs of our community to their attention, and
explain how budget appropriations and certain pieces of legislation can impact
those living with CF. Not convinced this
is for you? Let me outline the ways that
CF advocacy has touched my own life.</div>
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July 26th 2007, Brady came into this world. He was the first baby in Idaho to be picked up on the newborn screening program. That test was added to the newborn panel in Idaho the same week that Brady was born. After a positive screen came back, we performed genetic testing and he was diagnosed with CF before he was 3 weeks old. We were able to intervene immediately, and begin treatment with enzymes, airway clearance, CF vitamins, and other medicines that would help him grow and thrive. He didn’t have to become terribly ill and suffer potentially irreversible damage before we knew something was wrong. Obviously, the diagnosis was traumatic (especially in the throes of post-partum sleep deprivation and fluctuating hormones), but the benefits of early intervention are well studied, and we are eternally grateful that we had the opportunity to begin helping Brady fight this disease as soon as we could. The newborn screening program is up and running in all 50 states, which is awesome! <b> Newborn screening exists today because CF advocates worked for years on Capitol Hill to get it added to the newborn panel in each and every state. </b></div>
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When Brady was a baby, I learned that the Idaho Legislature was proposing legislation to cut a co-pay assistance program for adult patients with CF. The budget for this program was a mere drop in the bucket ($200,000 total annual budget), but a game-changer for adults needing assistance in Idaho. We already know that 1 in 4 CF patients sometimes skip doses of medication, or go without some prescriptions all together because of cost issues. Cutting this program would mean that many adults with CF in my state would lose the ability to get some of the drugs that they needed to manage their disease. It made $1000+ co-pays a monthly reality for many adult patients in Idaho. It caused severe anxiety and depression for some of those adults already struggling with advanced disease. It caused some adults who had previously been able to work part-time to lose/quit their jobs and become fully dependent on Medicaid or SSI for coverage of their life-sustaining drugs. It sucked (especially when I learned that the Idaho Legislature was creating a new “slush fund” with a $200,000 annual budget to pay lawyer fees when legislators found themselves in lawsuits that same year). Everything about it reeked. Though it wouldn’t affect Brady directly (the program was for adults only), he was on a similar state program for children, and<b> I realized that lawmakers were going to be making decision about his access to care and drugs</b>. I realized that many of the people making those decisions didn’t even know what cystic fibrosis was. I realized that unless I spoke up—they may never know. (Insert long rant of obscene language, and imagine me banging my head against a brick wall). <br />
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<tr><td class="tr-caption" style="text-align: center;">A newspaper article from our battle with the Idaho Legislature.</td></tr>
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If you are reading this blog, you might already know that my son Brady has been taking Kalydeco for over 3 years, and that it has changed our lives. But did you know that <b>the technology that led to the discovery of Kalydeco—“high-throughput screening,” was developed by the National Institutes of Health?</b> Did you know that targeting a genetic mutation for correction wouldn’t be possible without the NIH first mapping the human genome? Without the basic science that has helped us unravel the mysteries of our DNA, we wouldn’t even be able to DREAM of the kinds of “genetic modifying” drugs like Kalydeco that are being crafted today. Just to be clear—the CF Foundation funds nearly 100% of medical research for CF. The National Institutes of Health does NOT give a single dollar to the CF Foundation, or “orphan” (rare) disease research. They DO, however, fund basic science projects that enhance our understanding of genetics. They DO develop new technologies that could accelerate drug discovery for all diseases. They DO fund generalized research projects that may eventually be applicable to CF. The importance of funding the NIH has ALWAYS been a priority for CF advocates.</div>
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Take a look at our <a href="http://www.cff.org/research/DrugDevelopmentPipeline/">drug development pipeline</a>. It is jam packed with hopes and dreams. Hopefully, many of the drugs in clinical trials right now will be applying to the FDA for review in the coming years. When new drug applications are submitted, it is vitally important that the FDA has the resources they need to expertly and swiftly review those applications. The CF Foundation has worked for many years to build a relationship with the FDA, and enhance their understanding of our projects and goals. <b>Kalydeco was granted “priority review” status by the FDA, which served to expedite the approval process, and was given one of the fastest reviews in history</b> (less than 3 months from submission to approval!) Awesome! As you know, the quicker these miracles can get into patient hands…the better. </div>
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I hope I've made my case that CF advocacy is not about politics after all. I honestly believe that working to help shape our system is the most important way to ensure progress toward the cure and protect Brady's access to care and medicine. After attending the NACFC for the last 4 years, I am amazed and inspired by the science coming through the pipeline. We don't want roadblocks on the path to the cure. It is extremely important to educate our lawmakers on the unique needs of the cystic fibrosis community if we want a system that helps individuals and families with CF thrive... and YOU are the best experts in the world! It is much better to proactively troubleshoot problems that we foresee as we move toward the cure, than sit back and complain about a system that doesn't work for us when the damage is already done. CF advocacy is about <b>coming to the table and giving input about the policies that are shaping the future of healthcare</b>, With that in mind, I want to share more about the specific action items that March on the Hill advocates met with lawmakers about last week. </div>
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1) <b>Co-sponsorship of the Ensuring Access to Clinical Trials Act of 2015 (EACT) S139 H.R. 209</b></div>
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This legislation removes the sunset provision (expiration date) from the "Improving Access to Clinical Trials Act" (IACT), which was passed in 2010. IACT allows patients with CF and other rare diseases to receive up to $2,000 in compensation for participating in clinical trials without that compensation counting toward their income eligibility limits for SSI and Medicaid. Without this legislation, patients that we NEED to be able to participate in clinical trials, may not be able to, out of fear of losing their vital benefits. The Cystic Fibrosis Foundation is planning to fund 18 clinical trials next year--requiring 2500 patients to participate. When you consider the various exclusion criteria for those trials, and the fact that we only have about 30,000 CF patients nationwide--it is extremely important to remove this barrier to participation. IACT is set to expire in October. Advocates are trying to get EACT passed before this happens! This legislation costs a negligible amount of money, but is extremely important to ensure speedy and full enrollment of new clinical trials. EACT applies to all rare diseases, not just CF. Rare diseases impact nearly 1 in 10 Americans. According to the NIH, there are over 7,000 rare diseases affecting between 25-30 million people across the country. Rare disease researchers face real challenges recruiting enough patients to perform trials, and current treatment options are often very limited. Back in 2010, IACT received bipartisan support, and has allowed us to progress quickly forward with trial enrollment for the last 5 years. We really aren't asking for anything new at all with EACT--simply to remove the 5 year expiration date, and allow the law to remain permanent. Last week at March on the Hill, CF advocates from 38 states attended 273 meetings--and asking for support of this legislation was a priority in every one. EACT also has good bipartisan support...but we need to push it across the finish line here and now. You can help by taking action through the CF Foundation's advocacy page. Click, "<a href="http://www.cff.org/GetInvolved/Advocate/">Take Action Now</a>," then "Tell Congress to Protect Access to Clinical Trials," and follow the prompts. You can personalize the pre-written letter a bit with your CF connection, and send it directly to your representatives! This takes about 1 minute, and is a really effective way to let lawmakers hear your voice! It would be especially helpful if constituents from Texas could help us put some pressure on Senator Ted Cruz. I mean, the CF Foundation is funding the research. All we want is the opportunity to test our new amazing science in clinical trials! Is that too much to ask? NO!</div>
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2) <b>Support funding for the NIH and FDA</b>. </div>
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CF advocates are working to boost funding to the NIH this year and are asking lawmakers to approve a budget where the NIH receives at least $32 billion dollars in 2016. <span style="text-indent: -0.25in;">NIH funding has been flat
since 2002 (which translates to a DECREASE in funding each year when you take
inflation into account).</span><span style="text-indent: -0.25in;"> </span><span style="text-indent: -0.25in;">That means
that the NIH has been able to fund fewer and fewer interesting projects that
are seeking funding each year.</span><span style="text-indent: -0.25in;"> </span><span style="text-indent: -0.25in;">What is slipping through our fingers in those
</span><b style="text-indent: -0.25in;">missed opportunities</b><span style="text-indent: -0.25in;">?</span><span style="text-indent: -0.25in;"> </span><span style="text-indent: -0.25in;">What if one of those basic science projects might lead us
to a cure for CF?</span><span style="text-indent: -0.25in;"> </span><span style="text-indent: -0.25in;">It requires you to
take a big step back and take a look at the big picture, but we NEED to see
basic science research take a bigger priority in our government’s budget
appropriations.</span><span style="text-indent: -0.25in;"> </span><span style="text-indent: -0.25in;">Globally, America is
falling behind, and it is only going to get worse unless we change this
trend.</span><span style="text-indent: -0.25in;"> </span><span style="text-indent: -0.25in;">Investing in medical science is
an investment in the FUTURE of this country, and the future of our loved ones
with CF. Last week, CF advocates explained why NIH funding is important to the CF community on Capitol Hill, and asked them to sign the "Dear Colleage" letter circulating in both the House and the Senate to show their support of the $32 billion dollar budget. You can "<a href="http://www.cff.org/GetInvolved/Advocate/">Take Action Now</a>," then click "Protect our Progress Toward a Cure for CF," and follow the prompts. Once again--a minute of your time could make a big impact for families living with CF. </span></div>
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The FDA worked smoothly and quickly for Kalydeco. Why are we making FDA funding an issue? <span style="text-indent: -0.25in;">T</span><span style="text-indent: -0.25in;">he medical research community is soon going to be asking the FDA to
consider a huge number of new drugs in different ways than it ever has
before.</span><span style="text-indent: -0.25in;"> </span><span style="text-indent: -0.25in;">Historically, to be considered a
candidate for approval, the FDA has required long term trials with a large pool
of patients.</span><span style="text-indent: -0.25in;"> </span><span style="text-indent: -0.25in;">Obviously, these criteria
aren’t going to work for mutation specific CF drug trials.</span><span style="text-indent: -0.25in;"> </span><span style="text-indent: -0.25in;">As a rare disease, and with new therapies
targeted at specific genetic mutations, there may only be a few hundred (or
less) “qualified” patients that even exist worldwide!</span><span style="text-indent: -0.25in;"> </span><span style="text-indent: -0.25in;">It would be impossible to enroll huge numbers
of patients for </span><i style="text-indent: -0.25in;">individualized</i><span style="text-indent: -0.25in;">
genetic treatments for an already rare disease.</span><span style="text-indent: -0.25in;">
</span><span style="text-indent: -0.25in;">In 2012, CF advocates played an integral role in the passage of the
<a href="http://www.cff.org/aboutCFFoundation/PressRoom/PressReleases/2012PressReleases/6-20-Statement-House-Passes-EXPERRT-Act.cfm">EXPERRT Act</a>.</span><span style="text-indent: -0.25in;"> </span><span style="text-indent: -0.25in;">As part of this
legislation, a new “breakthrough” designation was created for drugs that treat
life-threatening diseases, for which there is no alternative.</span><span style="text-indent: -0.25in;"> </span><span style="text-indent: -0.25in;">Drugs that are granted breakthrough status,
are given a faster review schedule than ever before.</span><span style="text-indent: -0.25in;"> </span><span style="text-indent: -0.25in;">The legislation also enables the FDA to bring
in disease experts to consult on trials that don’t fit the old school criteria.</span><span style="text-indent: -0.25in;"> </span><span style="text-indent: -0.25in;">Passage of the EXPERRT act was a big victory
for the CF community, but we aren’t satisfied yet.</span><span style="text-indent: -0.25in;"> </span><span style="text-indent: -0.25in;">While CF is blazing the trail for this type
of drug design, an increasing number of disease communities are uncovering
genetic correlations of their own, and developing targeted therapies.</span><span style="text-indent: -0.25in;"> </span><span style="text-indent: -0.25in;">Personalized treatment is the future of
medicine for everything from CF to cancer and beyond. </span><span style="text-indent: -0.25in;"> </span><span style="text-indent: -0.25in;">The FDA is going to need a larger staff to
effectively review the growing number of new individualized drug applications
coming their way in the near future.</span><span style="text-indent: -0.25in;">
</span><span style="text-indent: -0.25in;">What a shame it would be to see amazing new drugs bogged down in delays
over a simple lack of time and personnel to perform safe and prompt reviews.</span><span style="text-indent: -0.25in;"> We want our future new drug applications to be considered with the same prompt expertise we saw with the Kalydeco approval. </span><span style="text-indent: -0.25in;">Bottom line is that the FDA is going to need
more money to function like we need it to in the very near future.</span><span style="text-indent: -0.25in;"> If you sent the "Protect our Progress Toward a Cure for CF" email, you are already done! Robust funding for both the NIH and FDA are included in that request!</span></div>
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<span style="text-indent: -0.25in;">3) <b>Join CF Caucus in the House of Representatives. </b> </span></div>
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The <a href="http://www.cff.org/GetInvolved/Advocate/CFCaucus/">CF Caucus</a> is sort of like a "club" that House Representatives can join to signify their support for the CF community. Follow the link to see if the people who represent you are members! Membership in the caucus raises awareness about CF, and issues that will impact patients and families living with the disease. We try to grow membership in this Caucus every year. Currently, there is no CF Caucus in the Senate. We don't have a specific action item in our CFF advocacy toolkit for this, but you are always free to email your own elected State officials and invite them to join the CF Caucus in the House (or find a great supportive Senator to START a caucus in the Senate!). </div>
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New issues come up all the time that could affect the CF community. To me, advocacy is about putting face on this disease, and letting our lawmakers know that their votes affect us as people. We are not just a number in a budget. Their votes mean something to us. We are the Mothers, Fathers, Grandparents, Sons, Daughters, Brothers, Sisters, Aunts, Uncles, Friends, and Patients dealing with this disease. As despicable as politics can seem at times...our lawmakers are actually just people. Most of them have families, and can imagine what dealing with CF must be like. I try to relate to them on a personal level to help them understand. When you are sitting face to face with them, the intimidation fades away, and it becomes apparent that they are actually very much like us. I encourage you to explore <a href="http://www.cff.org/GetInvolved/Advocate/AdvocacyToolkit/ActionMaterials/">CF advocacy efforts in your state</a>, and contact publicpolicy@cff.org with questions. </div>
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As a mother who has been lucky enough to see what a bright future new therapies like Kalydeco might hold for our CF community, I am determined to remove system barriers that might slow us down. I want EVERY patient and family to have a miracle like Kalydeco! I am honored and excited to serve as the CF Foundation's new National Advocacy Co-Chair with an awesome lady, Melissa Shiffman from NY. Melissa is an adult with CF, who is the mother of two beautiful children. As we are moving toward the goal of curing CF, there WILL BE OBSTACLES that require advocates to speak up. I believe with all my heart that if we want a system that works for us...If we want coverage that meets our needs...if we want to be fed...we must first come to the table! My life has been so touched by CF advocates. I feel like "Thank you" is a huge understatement. Besides, once you get bit by the advocacy bug, you can never quit! It is so empowering! Get involved in advocacy today and help protect the future for everyone with CF. Please "<a href="http://www.cff.org/GetInvolved/Advocate/">Sign up</a>" to receive the CF Foundation's advocacy newsletter, and action alerts! How about taking 30 seconds to advocate for CF patients RIGHT NOW by sending a tweet to Senator Ted Cruz in Texas asking him to support EACT?! Something like...<br />
<span style="background-color: white; color: #141823; font-family: Helvetica, Arial, 'lucida grande', tahoma, verdana, arial, sans-serif; font-size: 14px; line-height: 19.3199996948242px;"><br /></span>
<span style="background-color: white; color: #141823; font-family: Helvetica, Arial, 'lucida grande', tahoma, verdana, arial, sans-serif; font-size: 14px; line-height: 19.3199996948242px;">"The </span><a class="_58cn" data-ft="{"tn":"*N","type":104}" href="https://www.facebook.com/hashtag/cysticfibrosis?source=feed_text" style="background-color: white; color: #3b5998; cursor: pointer; font-family: Helvetica, Arial, 'lucida grande', tahoma, verdana, arial, sans-serif; font-size: 14px; line-height: 19.3199996948242px; text-decoration: none;"><span aria-label="hashtag" class="_58cl" style="color: #6d84b4;">#</span><span class="_58cm">CysticFibrosis</span></a><span style="background-color: white; color: #141823; font-family: Helvetica, Arial, 'lucida grande', tahoma, verdana, arial, sans-serif; font-size: 14px; line-height: 19.3199996948242px;"> community needs access to clinical trials, @SenTedCruz Pass S. 139!! </span><a class="_58cn" data-ft="{"tn":"*N","type":104}" href="https://www.facebook.com/hashtag/cfadvocacy?source=feed_text" style="background-color: white; color: #3b5998; cursor: pointer; font-family: Helvetica, Arial, 'lucida grande', tahoma, verdana, arial, sans-serif; font-size: 14px; line-height: 19.3199996948242px; text-decoration: none;"><span aria-label="hashtag" class="_58cl" style="color: #6d84b4;">#</span><span class="_58cm">cfAdvocacy</span></a><span style="background-color: white; color: #141823; font-family: Helvetica, Arial, 'lucida grande', tahoma, verdana, arial, sans-serif; font-size: 14px; line-height: 19.3199996948242px;"> @CF_Foundation"</span><br />
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Thank you wonderful people! </div>
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<tr><td class="tr-caption" style="text-align: center;">With my RAD new Co-Chair Melissa Shiffman on Capitol Hill last week!</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgBx8N37rFLPXMotySXAnJIgqJssnTECtk7bYe3X7ykdYkkOO_3YT6rOl_O8QuMr23pp0XFJ2LRZk2nYTYp_PMDlCK5yPwMpfmDpAYIVcH2vRhcqTUWnPfg_trU9D_yG8sH0MUFL1N3Ntw/s1600/advocacytalk.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgBx8N37rFLPXMotySXAnJIgqJssnTECtk7bYe3X7ykdYkkOO_3YT6rOl_O8QuMr23pp0XFJ2LRZk2nYTYp_PMDlCK5yPwMpfmDpAYIVcH2vRhcqTUWnPfg_trU9D_yG8sH0MUFL1N3Ntw/s1600/advocacytalk.jpg" height="225" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Chatting up CF advocacy at Sacred Heart's Family Ed day a few weeks ago. Do I ever shut-up? NOPE! <br />
And neither should you!</td></tr>
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Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com1tag:blogger.com,1999:blog-7535774120903384819.post-33180811743461874912014-10-14T08:57:00.000-07:002014-10-14T11:24:32.910-07:00The KIWI study:Ivacaftor for 2-5 year oldsI know that many of you have been anticipating this information. It wasn't presented until 4:00 p.m. on Saturday, and I apologize for the delay...<br />
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<span style="font-size: large;"><b><i>An Open-Label Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Ivacaftor in Patients Aged 2 to 5 Years With CF and a CFTR Gating Mutation: The KIWI Study</i></b></span></div>
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<span style="font-size: large;"><b>Jane Davies</b></span><br />
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Early intervention with a CFTR modifier like Kalydeco holds exciting potential. The hope is that the progressive organ damage associated with cystic fibrosis could be PREVENTED by early treatment. </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgLkkr0G-Y-odpbJk7P4eiWT4hB4IgwwX6gxDEizRvZ2cpx11_NIyvfUUMCe4h00A0he1q8NAZDqs1KVXV3NVnhsOB_odZV2W8hhUaapY5Qwjhzpo7GQPODomv47RwK89HORjpgQXE3PEE/s1600/20141011_155827.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgLkkr0G-Y-odpbJk7P4eiWT4hB4IgwwX6gxDEizRvZ2cpx11_NIyvfUUMCe4h00A0he1q8NAZDqs1KVXV3NVnhsOB_odZV2W8hhUaapY5Qwjhzpo7GQPODomv47RwK89HORjpgQXE3PEE/s1600/20141011_155827.jpg" height="360" width="640" /></a></div>
The study was designed mainly to assess the safety of Kalydeco. Patients were given either 50 mg. or 75 mg.(for patients over 14 kilos) Ivacaftor twice daily, in a newly designed granular powder formulation. The trial was not placebo controlled--all participants received the real drug. <br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh4DVtgViI08CSs_65KRfaYCnhWPsCtlCRB2vshOFcOEvNRlaqopJWYtoWjIZpRbFs333CmJh29AFPMGhK6RJVSBahLCnLzxlmrNYXVA1fNehg-8XRV8wTprH8O3KFuDvV1B7-30r_Ln_Y/s1600/20141011_155921.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh4DVtgViI08CSs_65KRfaYCnhWPsCtlCRB2vshOFcOEvNRlaqopJWYtoWjIZpRbFs333CmJh29AFPMGhK6RJVSBahLCnLzxlmrNYXVA1fNehg-8XRV8wTprH8O3KFuDvV1B7-30r_Ln_Y/s1600/20141011_155921.jpg" height="360" width="640" /></a></div>
While the study was open to children with any of the approved mutations listed on the slide below, the vast majority were enrolled with G551D.<br />
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Investigators collected data on pharmacokinetics, safety, sweat chloride, weight, BMI, Z-score, Fecal elastase-1 (measure of pancreatic function), Immunoreactive trypsinogen, and for the few kids in this age group that could reliably perform spirometry--FEV1. The majority of kids were unable to perform spirometry with good enough technique to be considered a valid measure.<br />
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You may recall that FEV1 was the primary endpoint in Ivacaftor trials in older kids and adults with CF. This trial was focused more on the safety of the drug in the younger group, and the utility of the new granular formula of administration. <br />
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The most notable adverse events reported in the study were the 5 patients that experienced increased liver enzymes during the Kalydeco trial (>8X normal levels). 3 of those patients chose to ultimately withdraw from the study. The speaker noted that all 5 of these patients entered the study with mild liver impairment. The speaker also commented on the wide number of health factors that can lead to increases in liver enzymes such as: illness, vaccinations, other medication such as antibiotics... Liver enzymes monitoring is recommended for everyone taking Kalydeco, and this group is no exception. During the question/answer period of the discussion, someone asked about the "high rates" of vomiting reported. I actually found myself laughing a bit at this question...because 2-5 year old kids vomit a lot, whether they have CF or not. Kids in this age group are fairly notorious for teething, getting viruses, not chewing up their food well enough, or the thousand other reasons they might find to puke. The investigator seemed to be thinking along the same basic lines, and felt that if a placebo arm of the study had existed, similar rates of vomiting would have presented. No opthomological effects (cataracts) were observed.<br />
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<img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjz-dqFVDEWXHU7tMmNTA5AC4WB0DXtutS-hxyrcxoLco3dzb2q_SKgKdw7MGrZcHcYEOS0a421irhT11zn6xkk9clDXigM-sH_xLErlqR-E9fUC6Z6vDVLleT27dCKYIqmIV3xnsXI-PE/s1600/20141011_160830.jpg" height="360" width="640" />Researchers were astonished to discover the pancreatic function improvements in these patients, as witnessed in fecal elastase examination. An audience member asked if patients were able to reduce or stop enzymes, and the speaker responded that they had not been instructed to, but she had heard that some patients had. Another person asked about the potential to increase the risk of pancreatitis by giving patients "partial pancreatic function." The speaker responded that she couldn't really answer that question (because she didn't know), but that there was no evidence of those issues in the clinical trial period. Investigators were also surprised to see changes in IRT levels, and weren't exactly sure what the clinical implications of these changes might be. </div>
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I am extremely excited to see Kalydeco reach this younger population group. If you follow my blog, you probably already know how strongly I believe in early intervention with CFTR modifiers to PREVENT the organ damage associated with cystic fibrosis, and enable these individuals to live longer, healthier, and more productive lives than ever before...<br />
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In closing, I want to share this testimony that I just sent to the FDA. They are currently reviewing the application of Kalydeco for R117H. There is plenty of evidence that Kalydeco works to restore CFTR function for this mutation, but R117H is typically considered a "milder" mutation of CF. These individuals don't often present with serious lung disease until later in life, and did not show the same level of statistical FEV1 improvement in clinical trials. I feel strongly that people shouldn't have to get sicker, as the only means to make themselves eligible to become well. It just doesn't make sense. I want to see EVERY PATIENT THAT CAN BENEFIT, whether you are a 2 year old with G551D, or a 30 year old with R117H, have access to Kalydeco. I want to see patients prevent damage with this drug and enhance the quality of their lives. I encourage anyone who has experience with Kalydeco, or who has R117H to <a href="http://www.fda.gov/AdvisoryCommittees/Calendar/ucm417332.htm">submit testimony</a> of their own. I also hope that parents of children 2-5 with approved gating mutations are poised and ready to make similar arguments in the coming weeks if testimony is requested as part of the FDA review process. Submissions for R117H should be sent to Cindy Hong: PADAC@fda.hhs.gov by <b>October 16th</b>. This is what I said:<br />
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<i>My name is Rebecca Schroeder, and I have a 7 year old with cystic fibrosis named Brady. Brady started taking <span class="yiv7680982289" id="yiv7680982289misspell-1">Kalydeco</span> on February 10<span class="yiv7680982289" id="yiv7680982289misspell-2">th</span>, 2012, at the age of 4 1/2. Though he had maintained his lung health fairly well up until that point in time, he still spent approximately 2 hours a day on breathing and airway clearance treatments to maintain that function. He also suffered from the classic pancreatic insufficiency associated with CF, which caused him considerable discomfort in the form of digestive dysfunction. For Brady, cystic fibrosis also brought serious upper respiratory inflammation that manifested as sinus polyps. A CT scan revealed that the polyps were growing so aggressively, that they had begun to thin and shift the fragile bones in his face--and threatened to break through his eye socket, leading to possible blindness or brain damage. Brady had absolutely zero sense of smell. He underwent sinus surgeries as a 4 year old before beginning <span class="yiv7680982289" id="yiv7680982289misspell-3">Kalydeco</span>, and took frequent bursts of oral <span class="yiv7680982289" id="yiv7680982289misspell-4"><span class="yiv7680982289" id="yiv7680982289misspell-4"><span class="yiv7680982289mark" id="yiv7680982289misspell-4">Prednisone</span></span>, performed 3X daily steroid/antibiotic sinus rinses</span> in an attempt to control the swelling. Quality of life was poor, to say the least. We did everything we could to battle the progression of the disease, but the symptoms he suffered through everyday made all of our lives hell, despite our best efforts. Watching your child struggle to breathe is an indescribable torture. </i></div>
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<i>Everything changed the day <span class="yiv7680982289" id="yiv7680982289misspell-5">Kalydeco</span> arrived at our door. Within a few days of beginning therapy, we began to see Brady's health completely transform. As the committee is likely aware, <span class="yiv7680982289" id="yiv7680982289misspell-6">Kalydeco</span> treats cystic fibrosis at the root cause of disease, by restoring <span class="yiv7680982289" id="yiv7680982289misspell-7">CFTR</span> protein function to all the affected organs in the body--lungs, pancreas, sinuses, and the entire gut. Almost overnight, the serious sinus polyps that Brady had battled on a daily basis for YEARS began to recede, and he discovered his sense of smell for the first time, in a long time. Before <span class="yiv7680982289" id="yiv7680982289misspell-8">Kalydeco</span>, his sinuses were completely blocked. I heard every breath he struggled through at night, because his bedroom is right next to mine. He would frequently snore/snort himself awake during this struggle, making restful sleep impossible. After 3 days of <span class="yiv7680982289" id="yiv7680982289misspell-9">Kalydeco</span>, all the awful sounds coming from his room stopped. Brady's breathing became so effortless and silent, and he slept so soundly--that it scared me to death! My husband and I found ourselves running into his room several times, every single night, to ensure that he was still breathing at all. The change was truly remarkable. In the 6 months before beginning <span class="yiv7680982289" id="yiv7680982289misspell-10">Kalydeco</span>, Brady had seen his <span class="yiv7680982289" id="yiv7680982289misspell-11">Ear/Nose/Throat</span> specialist 11 times. Post-<span class="yiv7680982289" id="yiv7680982289misspell-11">Kalydeco</span>, he has only seen that Dr. ONCE--to document the complete disappearance of symptoms. Additionally, we observed that Brady's energy level shot through the roof, his digestive function improved dramatically, and the constant stomachaches disappeared. He began to grow and gain weight beyond our wildest dreams. He began to smile more. Furthermore, the mucus in Brady's lungs became thin and watery, rather than thick and sticky as it had been before. The mucus began to function as the vital organ lubricant it was designed to be, and has maintained his lungs FREE from the invading organisms associated with CF mortality. His CT scan shows that he is FREE of <span class="yiv7680982289" id="yiv7680982289misspell-12">bronchiectasis</span> (irreversible widening and loss of elasticity of the airways). Brady is now FREE from the hours of daily breathing treatments he used to rely on as ammunition in a losing battle... Today, Brady has those two hours he used to spend doing breathing <span class="yiv7680982289" id="yiv7680982289misspell-13">treatments</span> each day to simply play, and just be a kid. Because Brady hadn't suffered excessive lung damage when this miracle drug was added to his regimen, he no longer has to face an inevitable future of progressive lung disease. I don't EVER anticipate having to face the painful prospect of a double lung transplant, which is unfortunately, the only way to extend life for most individuals with CF. </i></div>
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<i>I feel that I am in a unique position to provide valuable testimony to the board considering <span class="yiv7680982289" id="yiv7680982289misspell-14">Kalydedo</span> for approval for the R117H mutation. I have attended the North American Cystic Fibrosis Conference for the last 4 years, and seen proof that <span class="yiv7680982289" id="yiv7680982289misspell-15">Kalydeco</span> works to restore <span class="yiv7680982289" id="yiv7680982289misspell-16">CFTR</span> protein function for this mutation. R117H is considered one of the "milder" CF mutations, which means that serious lung disease often doesn't present until later in life. These patients ultimately still suffer the same fate as other mutations that have already have access to <span class="yiv7680982289mark" id="yiv7680982289misspell-16">Kalydeco</span>, like G551D--but the later onset of symptoms provides an ideal window of opportunity for intervention in disease progression. I contend that the statistical improvements in <span class="yiv7680982289" id="yiv7680982289misspell-17">FEV</span>1 were smaller for this group of patients, because their lung function was higher to begin with. Lung function must first be lost, in order to make those gains possible. If large jumps in <span class="yiv7680982289" id="yiv7680982289misspell-18">FEV</span>1 are the main criteria for approving a disease altering therapy like <span class="yiv7680982289" id="yiv7680982289misspell-19">Kalydeco</span>--many of the patients that stand to benefit MOST, will be excluded. Patients like Brady, who could represent the first generation of individuals to LIVE a normal life, and successfully manage the symptoms of CF would be denied their miracle. If you took Brady to the lab today, and performed the sweat test on him--a diagnostic test which is correlated to <span class="yiv7680982289" id="yiv7680982289misspell-20">CFTR</span> function--he would test negative for cystic fibrosis. The drug has changed the way his body functions on a fundamental level, and will likely add decades of time, and immeasurable quality to his life. I urge you to consider the implications of denying patients this drug in the <span class="yiv7680982289" id="yiv7680982289misspell-21">abcense</span> of a larger jump in <span class="yiv7680982289" id="yiv7680982289misspell-22">FEV</span>1. That requirement is akin to demanding that these patients first become more ill, before they are eligible to become well. One thing is for sure, if you wait long enough, the damage is guaranteed to happen in CF. With the median life expectancy hovering around 40 years old, time is not a luxury we enjoy in this community. </i></div>
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<i>I beg you to examine the evidence on <span class="yiv7680982289" id="yiv7680982289misspell-23">Kalydeco's</span> powerful impact on <span class="yiv7680982289" id="yiv7680982289misspell-24">CFTR</span> function for this group, as well as the additional positive outcomes I have detailed. After seeing the positive effects of this drug in my own child, the thought of delaying or denying access to R117H patients is <span class="yiv7680982289" id="yiv7680982289misspell-25">unconscionable</span>. I am desperate to see this remarkable innovation reach R117H patients. <span class="yiv7680982289mark" id="yiv7680982289misspell-25">Kalydeco</span> would help these individuals, and could make them part of this new generation, who easily outlive their parents.</i></div>
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<div id="yui_3_16_0_1_1413298478918_5830" style="font-family: HelveticaNeue, 'Helvetica Neue', Helvetica, Arial, 'Lucida Grande', sans-serif; font-size: 12px;">
<i>Thank you so much for your time and consideration. Sincerely,</i></div>
<div id="yui_3_16_0_1_1413298478918_5829" style="font-family: HelveticaNeue, 'Helvetica Neue', Helvetica, Arial, 'Lucida Grande', sans-serif; font-size: 12px;">
<i>Rebecca Schroeder</i></div>
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Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com7tag:blogger.com,1999:blog-7535774120903384819.post-32853954348132020922014-10-12T10:11:00.000-07:002014-10-12T10:33:45.115-07:00Beyond Small Molecules--Gene Editing Strategies Provide Real Hope to Truly "Leave No Mutation Behind." NACFC 2014Successful rescue of CFTR function with small molecules like Kalydeco, or corrector/potentiator combination therapies (VX-809/VX-770) hold a lot of promise for the immediate future of altering the course of CF disease. The tricky part about small molecule therapy, is that different mutations produce their own unique issues. As we know already, Kalydeco monotherapy is effective for a small percentage of CF mutations, but produces little or no effect at all, in others. Finding novel combinations of correctors and potentiators to successfully rescue robust amount of CFTR protein function for the myriad of mutations will not be a simple task. Each year, I hear about dozens of new corrector and potentiator compounds that may be combined in different ways to successfully affect CFTR rescue. After seeing the potential of this type of therapy in my own son, I am anxious to see more small molecules treatments successfully reach the market. <br />
<br />
The small molecule approach can be a very powerful way to impact CFTR function, but still represents a temporary fix for a permanent problem. For patients like Brady, Kalydeco might be considered a "one day cure." As long as he maintains sufficient levels of Ivacaftor pumping through his veins, his body doesn't really realize it has CF..., BUT, if he were to stop swallowing those expensive little blue darlings, his CF symptoms would return quickly. Because of the temporary nature of the effects, small molecules don't really fit the bill as a true cure. While the CFF has millions of dollars invested in the development of new small molecules, they are also looking even further toward the future. Ultimately, we would all love to see a LIFETIME cure, rather than a ONE DAY cure. True to the "venture philanthropy" model that The CF Foundation has made famous, they are poised to make considerable investments in new exciting fields of research that could yield that lifetime cure that we all dream of, for each and every person with cystic fibrosis--regardless of their genetic mutations. I was disappointed that the UK Gene Therapy Trial results were not presented at this meeting as scheduled, but there are plenty of other new technologies to get REALLY excited about.<br />
<br />
<b><span style="font-size: large;"><i>Symposium Session 8: Gene Editing Strategies for Therapy and Research</i></span></b><br />
<br />
In this session, two technologies were described to manipulate genes such as CFTR. What makes these techniques so attractive is that they <b>have the potential to be tailored to treat diverse cystic fibrosis mutations</b>. These techniques can be thought of as "mutation agnostic," and could provide functional results for the multitudes of CF mutations, no matter how rare or complex the dysfunction.<br />
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1) Genome editing by the CRISPR/Cas9 system<br />
2) RNA editing--where mutations in messenger RNA are corrected without modification of the genomic DNA<br />
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<span style="font-size: large;"><b><i>Functional Repair of CFTR by CRISPR/Cas9 in Intestinal Stem Cell Organoids of CF Patients</i></b></span><br />
Jeffrey Beekman<br />
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To perform this study, adult intestinal stem cells were obtained from rectal biopsies of adults with CF. Just to be perfectly clear--embryonic stem cells were not required in this research. The tissue samples obtained from the rectal biopsies were then taken into the lab, where they were manipulated to create intestinal organoids for experimentation. Most people have heard a lot about changes in sweat chloride levels as a measure of CFTR function. Over the last several years, I've seen more and more evidence that, while correlated with CFTR function, sweat chloride levels may not paint the most accurate picture of how much functional CFTR is being rescued. A better way to directly measure CFTR channel function is to examine intestinal organoid swelling. <br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEisPgoDW0kjxTV9aV6qj-Vw2tNRwyVbE1NwST_cFgscAhocVxZmdd9o_iyM4heiEqw1wJAIwP6HuDTM6ZCRNEDll4aP2Up_J_ZZUxSBimSVlydXq_Sie3CBH5dbFWbZhHVERPjBbFDEFwQ/s1600/20141010_110658.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEisPgoDW0kjxTV9aV6qj-Vw2tNRwyVbE1NwST_cFgscAhocVxZmdd9o_iyM4heiEqw1wJAIwP6HuDTM6ZCRNEDll4aP2Up_J_ZZUxSBimSVlydXq_Sie3CBH5dbFWbZhHVERPjBbFDEFwQ/s1600/20141010_110658.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">This slide details the methods used to grow organoids from adult stem cells. </td></tr>
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CFTR function can be directly measured via the amount of swelling that intestinal organoid cells exhibit. The amount of swelling can be directly correlated to CFTR function. This has been found to be a much more accurate measure of CFTR channel activity than sweat chloride measurements.<br />
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For the record, <b>CRISPR</b> stands for <b style="background-color: white; color: #252525; font-family: sans-serif; font-size: 14px; line-height: 22.3999996185303px;">clustered regularly interspaced short palindromic repeats--</b><span style="background-color: white; color: #252525; font-family: sans-serif; font-size: 14px; line-height: 22.3999996185303px;">specific targets on a gene, containing short repetitions of base sequences, followed by short segments of "spacer" DNA. <b>Cas9</b> is a single DNA targeting enzyme that serves to "code" for proteins related to CRISPRS. In simpler terms, the CRISPR can be thought of as the specific portion of DNA targeted for alteration (the section where we find the presence of the CF mutation). Cas9 can be thought of as a tiny pair of scissors, programmed to make a cut in the strand of DNA at precisely the right spot.</span><br />
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Here, the CRISPR-Cas9 gene editing system was used to repair the CFTR-F508 target. Once the double strand cut is made in the DNA by Cas9, the DNA undergoes homologous recombination--or automatic repair to "fix" the break. After recombination, the repaired DNA no longer contains the problematic CF mutation.</div>
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Using this method, researchers were able to restore functional swelling of the organoids in homozygous DF508, indicating restored CFTR function. <br />
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This work is very preliminary...but extremely exciting. This experiment serves as proof-of-concept for "regenerative medicine" approaches of CF using gene-corrected adult stem cells. In addition, this study shows that intestinal organoid swelling can be an effective mode of measuring CFTR function for future studies. At this point, researchers will need to work on improving the efficiency of correction, which is still very low. They seem confident that refinement of technique can produce much higher efficiency in future studies.<br />
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<span style="font-size: large;"><b><i>Correction of Genetic Mutations By Site-Directed RNA Editing</i></b></span><br />
Joshua Rosenthal<br />
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The description of RNA editing involves a lot of technical
jargon, so I am going to lay this out in two totally different ways—first the scientific
version, and then my layman’s translation. <o:p></o:p></div>
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<u>Version 1:<o:p></o:p></u></div>
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<u>A</u>denosine <u>d</u>eaminases that <u>a</u>ct on <u>R</u>NA
(ADARS) are a family of enzymes whose activity resembles a natural form of
targeted mutagenesis. Biochemically,
ADARS convert adensosine to inosine—a nucleotide that is read as guanosine
during translation. ADARS are modular
enzymes with distinct domains that perform different functions. At one terminus, they contain a deaminase
domain that catalyzes the deamination of adenosine to inosine. At the other end, a number of double-stranded
RNA binding motifs (dsRBMs) are found. These
dsRBMs bind to the tertiary structures in pre-mRNAs. It is problematic to manipulate the ADARS
targeting mechanism, so researchers decided to replace ADAR’s dsRBMs (the
binding end of the enzyme) with a more easily manipulated, antisense RNA
oligonucleotide—which could be easily directed to bind with any primary
sequence along an RNA. Researchers found,
that when this antisense RNA oligonucleotide was joined with the dsRBM (via a
small bacteriophage binding protein), they could selectively target and edit a
single adenosine. When editing occurs in
mRNAs, codons can be recoded and the changes can alter the protein
function. For example, mutations which
cause premature termination codons (UAA, UGA, UAG) could be recoded to
tryptophan (UGG) to achieve successful protein read-through. To test their editing system, and provide
proof of concept for encoding CFTR, researchers selected the W496X mutation,
which contains an early “stop” codon. In
vitro, they showed that their system of directed editing could correct W496X
with near perfect efficiency. In <i>Xenopus </i>oocytes, the genetically encoded
version of their editase corrected CFTR mRNA, restored full-length protein, and
reestablished functional chloride currents across the plasma membrane. In human cell lines (grown in lab), their
editing system was able to correct a non-functional version of enhanced green
fluorescent protein (eGFP) with a premature termination codon. The next step is to try and correct
endogenous CFTR W496X, and other CFTR mutations caused by G-to-A transition, in
epithelial cell lines. <o:p></o:p></div>
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<u>Version 2:<o:p></o:p></u></div>
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Since I am sitting in the airport, I will also describe RNA
editing like this—Imagine DNA as our flight map. This “map” tells the pilot what the final
destination is, and how to get there.
The RNA can be thought of as the “pilot” of our flight, whose job is to
follow the map, and deliver passengers where they are supposed to go. Of course, the pilot (RNA) knows all the
details about the trip: how high to take the plane, when to make turns, and how
to land at the final destination. The
problem is that sometimes the pilot shows up drunk, and causes the flight to
crash and burn. In that case (as with
premature stop codon CFTR mutations), none of the passengers reach their
destination. ADARS (paired with the
antisense RNA oligonucleotide) can be thought of as “hijackers,” secretly coming
onboard and forcefully changing the details of the flight plan. They mask the pilot, steal his uniform, pilot
hat, and cute little wings (to look “official” and keep the passengers calm)
and take the plane to a different destination than originally planned. Fortunately, the hijackers (in the case of
RNA editing) are actually pretty cool (especially compared with to the passed
out drunk previously in charge), and instead of taking the blissfully unaware passengers
to their originally scheduled work conference in Shittsville, (no CFTR protein
produced) decide to redirect the flight to an all-inclusive resort in The
Cayman Islands (functional, full-length CFTR).
<o:p></o:p></div>
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<o:p></o:p></div>
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I hope I was able to convey the fundamental concept behind
this new research, because site directed RNA editing is truly a very promising
and exciting strategy to correct a broad variety of genetic mutations, in both
CFTR as well as other proteins. The
correction of genetic mutations at the mRNA level is attractive for several
reasons. <o:p></o:p></div>
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<!--[if !supportLists]-->1<span style="text-indent: -0.25in;">)</span><span style="font-size: 7pt; text-indent: -0.25in;"> </span><span style="text-indent: -0.25in;">Compared to DNA, mRNA is easily accessible
(genomic DNA is sequestered in the nucleus and tightly bound by histones).</span></div>
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<!--[if !supportLists]-->2)<span style="font-size: 7pt;"> </span><!--[endif]-->Mature mRNA is in the cytoplasm. The delivery of a site-directed editor to
mRNA would only entail crossing a single membrane.<o:p></o:p></div>
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<!--[if !supportLists]-->3)<span style="font-size: 7pt;"> </span>Because RNA is transient (where DNA is not),
off-target edits (targeting mistakes) are less dangerous.<o:p></o:p></div>
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<!--[if !supportLists]-->4)<span style="font-size: 7pt;"> </span>Site-directed RNA editing does not affect mRNA
expression level (expression level must be precise—as both under-expression or
over-expression can result in disease). </div>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj9YXtFFpzy5vstfHulms2u8Yr2En5_8EQtchEocsjSXrgGCy8t6pB4JoneE7QWqPwzeL59nHfhpcUJ3MKARItJvjDdzrTJ5jEr4nDc91DG6Jct_U-4rM5jh7BgtckjJA-FnrF-Eo5d0Rg/s1600/cayman.jpg" imageanchor="1" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj9YXtFFpzy5vstfHulms2u8Yr2En5_8EQtchEocsjSXrgGCy8t6pB4JoneE7QWqPwzeL59nHfhpcUJ3MKARItJvjDdzrTJ5jEr4nDc91DG6Jct_U-4rM5jh7BgtckjJA-FnrF-Eo5d0Rg/s1600/cayman.jpg" height="401" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;"><span style="font-size: small; text-align: start; text-indent: -24px;">I've never actually visited The Cayman Islands before...but it seems like a really nice place.<br /></span></td></tr>
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Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com2tag:blogger.com,1999:blog-7535774120903384819.post-20892356569461259012014-10-10T23:24:00.000-07:002014-10-11T11:12:31.246-07:00LIVING with CF--updates from NACFC 2014<div>
The NACFC discussions that receive the most attention are typically geared toward the scientific developments. Obviously, I care deeply about progress toward a cure, but I try to balance those technical talks with some information on ways that we--as a community of patients and families, might be able to have a real positive impact on health through the informed choices we make today. </div>
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<span style="font-size: large;"><i><b>The Relationship Between Exercise Capacity and Glucose Tolerance in a Pediatric CF Population Not Diagnosed with Cystic Fibrosis Related Diabetes.</b></i></span> <br />
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<span style="font-size: large;">Foster, K.E. Cincinnati Childrens Hospital</span><br />
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Hopefully, most people recognize that regular exercise can provide numerous health benefits to ANYONE. Regular exercise is especially important for those with CF. CF related diabetes (CFRD) is a frequently occurring complication of cystic fibrosis, and is associated with greater decline in lung function, poorer nutritional status, and lower life expectancy. In this discussion, Foster examined the connection between exercise capacity, and the ability to successfully regulate blood sugars. </div>
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Foster measured both exercise capacity, and glucose tolerance (via oral glucose tolerance testing) in 50 patients, and discovered a correlation between low exercise capacity, and increased 2 hour blood glucose values. This suggests that patients with low exercise capacity have poorer glucose tolerance. Foster speculates that working to improve exercise capacity may help delay the onset of CFRD via improved blood sugar control. </div>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgu1SFm3Fpf8ZBP5cNgeWh1uuBrmSqwNeiwX6NijOQ9Dzv9JGGoFgaO0gBVgr6rBhxg1gvn5zcOvTEVEsgHaJfxxaeU2Wl5wZFYWXOGPBEkrBQvnygZK8Hd6A7Ax1jCfzxu1zlQYFtDuXQ/s1600/20141009_110843.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgu1SFm3Fpf8ZBP5cNgeWh1uuBrmSqwNeiwX6NijOQ9Dzv9JGGoFgaO0gBVgr6rBhxg1gvn5zcOvTEVEsgHaJfxxaeU2Wl5wZFYWXOGPBEkrBQvnygZK8Hd6A7Ax1jCfzxu1zlQYFtDuXQ/s1600/20141009_110843.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">As you can see in this slide, there isn't hard data on this correlation, but rather, a strong suspicion that blood sugar control may be improved with regular exercise--leading to a delay in the onset of CFRD. </td></tr>
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Since I personally believe strongly in the value of exercise in health maintenance, I want to hammer the point home with one more discussion:</div>
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<span style="font-size: large;"><b><i>Yoga Improves Posture and Muscular Performance in Adult Persons with Cystic Fibrosis</i></b></span></div>
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<span style="font-size: large;">Scott Russell, University of Southern California</span></div>
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"<i>Persons with cystic fibrosis are prone to posture dysfunction, in part due to pulmonary hyperinflation and chronic coughing which can lead to injury, chronic pain disorders, vertigo, headaches, balance dysfunction, increased risk for vertebral fractures, and loss of physical functioning. The purpose of this study is to investigate the effects of Hatha yoga on posture, neuromuscular performance, and self-reported psychometric measures."</i></div>
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In this small study, patients agreed to participate in twice weekly, 90 minute, outdoor yoga sessions over the duration of 8 weeks. A couple of important points worth noting:</div>
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1) Strict infection control guidelines were observed--persons with CF were each provided with their own (vs. shared) yoga props, and were equipped with hand sanitizer gel, tissues, etc... Yoga was also practiced in an open, outdoor area and the "6 ft. rule" was observed due to multiple CF participants in the same class. Of course, if you decide to take up yoga, it is unlikely that you would be surrounded by other CF patients, and such strict precautions may not be required. </div>
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2) Russell made sure to note that practice of yoga for CF patients often requires modification of poses to <b>avoid the "head down" position, or "inversions,"</b> which can aggravate acid reflux/GERD for many patients. It is very important to educate the instructor about the need for these modifications, since an increase in acid reflux symptoms would be an undesired effect, and could lead to a worsening, rather than an improvement in lung and postural health.</div>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjmCoVixoRfutPwLwqOdtEZPT_K5OhFXil63Wc0qF4H34RiVVHkoHozynFc896a-sQQrre0co2qtVK1KRptlNO0Iw6VgFn6gOd4gh51IK2SEaIzEeWi-bv7eIcxCO5GYqrTiiuoGQwHXn8/s1600/20141009_111555.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjmCoVixoRfutPwLwqOdtEZPT_K5OhFXil63Wc0qF4H34RiVVHkoHozynFc896a-sQQrre0co2qtVK1KRptlNO0Iw6VgFn6gOd4gh51IK2SEaIzEeWi-bv7eIcxCO5GYqrTiiuoGQwHXn8/s1600/20141009_111555.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">This is hard to read, but it says that the primary aims of this study are to discover 1) the effects of yoga on pulmonary functional, and chest wall mobility, 2) the effects on physical function and posture, and 3) effects on scapulothoracic posture. Self-reported psychometric measures regarding quality of life were also recorded. Ultimately, Russell wanted to determine the SAFETY and POTENTIAL BENEFITS of yoga for persons with CF.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiQlUEkhXnzPLN4lf2qPhPE3p1hfL8TAdb2F-eEk9Yc6SdCVMe3NKvUaHTCy3oNgqkZU_NvN0Ta8-gu45iOYiuXQMFKHjQN2vSI1MnnWxyaSSiNV389cTfbsJn5LqN1dG61xC0M12Phdhs/s1600/20141009_111611.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiQlUEkhXnzPLN4lf2qPhPE3p1hfL8TAdb2F-eEk9Yc6SdCVMe3NKvUaHTCy3oNgqkZU_NvN0Ta8-gu45iOYiuXQMFKHjQN2vSI1MnnWxyaSSiNV389cTfbsJn5LqN1dG61xC0M12Phdhs/s1600/20141009_111611.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">These are examples of the "head down" positions that should be <b>AVOIDED</b> if you suffer from acid reflux/GERD.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjUySfMa4Cz8zcCrmyee_OS_iFvYD3kmQNRx4dW_AWFwlppJJEDUkrFG56mYa-hj51q7WmfZ12LJ7ARpT7F_1uIkpYxeODShg_4G05ydWEQ2SuRskxykn-EpzZ3AaeVzbQxAc2XZQnJXZU/s1600/20141009_111647.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjUySfMa4Cz8zcCrmyee_OS_iFvYD3kmQNRx4dW_AWFwlppJJEDUkrFG56mYa-hj51q7WmfZ12LJ7ARpT7F_1uIkpYxeODShg_4G05ydWEQ2SuRskxykn-EpzZ3AaeVzbQxAc2XZQnJXZU/s1600/20141009_111647.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Here we see an example of a modified downward-facing dog position. Note that the trunk and head stay parallel to the ground, rather than the typical head down positioning. A few extra props may be helpful for the appropriate modifications</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiYZ5dT_JbjkLbl_BtwDSD4RfB6SpzOFL95UVvmCuxll5os0O6I6HF24O9Q0LxCD_JHbKVlNtPuCr_5WpOnnjAGd6P-Oi_i3ATSBNgw_M5H81ucHxt-NOHFFOVB5a1ESxeQ_NV3IY0y4S4/s1600/20141009_111719.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiYZ5dT_JbjkLbl_BtwDSD4RfB6SpzOFL95UVvmCuxll5os0O6I6HF24O9Q0LxCD_JHbKVlNtPuCr_5WpOnnjAGd6P-Oi_i3ATSBNgw_M5H81ucHxt-NOHFFOVB5a1ESxeQ_NV3IY0y4S4/s1600/20141009_111719.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Russell provided an example of the poses used by the instructor in the intervention. </td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiX_OS8_pQKlmvJjJSelv0wPotknE7WNY_ewjPumKXQEJTNwZ2lQo4kpxs3zdpJz-N1m99wgL-TVtWdzYd2-22DKzbL0EwFNTaYjsouz2G-39JAXm3aFQPObnxrf1HMy33ftkT5aYhiOFQ/s1600/20141009_111822.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiX_OS8_pQKlmvJjJSelv0wPotknE7WNY_ewjPumKXQEJTNwZ2lQo4kpxs3zdpJz-N1m99wgL-TVtWdzYd2-22DKzbL0EwFNTaYjsouz2G-39JAXm3aFQPObnxrf1HMy33ftkT5aYhiOFQ/s1600/20141009_111822.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">The results showed an improvement in chest wall excursion after 8 weeks of the yoga intervention.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgXz33HK_zSO_9JgJKkYx6_PE-xYzuMVOkqYVTvDiTHrhwjYDvyR1KEprHvxgUqJ2XndPwQa0dU47Mzc2UDESMS7TeDfyZNnDT687bHuMP06AIK8k_c2sWhjaFu8lzaazxRaf_z8cKWFtE/s1600/20141009_111844.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgXz33HK_zSO_9JgJKkYx6_PE-xYzuMVOkqYVTvDiTHrhwjYDvyR1KEprHvxgUqJ2XndPwQa0dU47Mzc2UDESMS7TeDfyZNnDT687bHuMP06AIK8k_c2sWhjaFu8lzaazxRaf_z8cKWFtE/s1600/20141009_111844.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Scapular positioning was also improved--positive effects on posture. </td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEitjT7PXGJNVzLNBx9sri6TpmOj_l1fNTqjLtVPd3NP7lolbi2X6RggjFK0o0H4cPLt83sWqLVb0ynlvOWAXvIaDXyZS9NQKE3f3Hj-tNi6C4jqElCAaijpmRG8keukjoHEBwFBga6Q7bo/s1600/20141009_111858.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEitjT7PXGJNVzLNBx9sri6TpmOj_l1fNTqjLtVPd3NP7lolbi2X6RggjFK0o0H4cPLt83sWqLVb0ynlvOWAXvIaDXyZS9NQKE3f3Hj-tNi6C4jqElCAaijpmRG8keukjoHEBwFBga6Q7bo/s1600/20141009_111858.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Patients showed improvements in the "Sit to Stand Test" and several other fitness measures.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgtrlENujmD0KOED-ohb0961o2LCMgFhgzAda7m8-SWsT7Hv-armL9klqkFu4J_2SlskVshWe_SSkz9tPznNmmPfuhBfp5H7LdRXIt_z9tlZy5S5P5OoVWI89UAcwuuld4pshkMmyb-xP4/s1600/20141009_111927.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgtrlENujmD0KOED-ohb0961o2LCMgFhgzAda7m8-SWsT7Hv-armL9klqkFu4J_2SlskVshWe_SSkz9tPznNmmPfuhBfp5H7LdRXIt_z9tlZy5S5P5OoVWI89UAcwuuld4pshkMmyb-xP4/s1600/20141009_111927.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Patients had improved self-reported attitudes toward their weight/body image.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjOfXl6jcFMzOlNOxINiqpqWMMEgOmZVm3DLMX5GQFdXvHD09gQayIjcDmRhmMp_bdBIDmqGBMFWSUUa7VAuUu0ti3q8dPh10Z0cwF5iQEv0E2kLOadD46WUXlvbRLHlmOBMQAWvuwVnnc/s1600/20141009_112058.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjOfXl6jcFMzOlNOxINiqpqWMMEgOmZVm3DLMX5GQFdXvHD09gQayIjcDmRhmMp_bdBIDmqGBMFWSUUa7VAuUu0ti3q8dPh10Z0cwF5iQEv0E2kLOadD46WUXlvbRLHlmOBMQAWvuwVnnc/s1600/20141009_112058.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">As I mentioned earlier, this was a small study, but I appreciate that we are discussing topics like this AT ALL, so I wanted to report on it anyway! It is my blog, and I do what I want! :)</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh5ZAzhZMxlCkP6z_UY8KaJATx5yNBTRTCkZFGzgp_zquKxwQ3BWBhIWkYLXO_uM3vMtMGQiNM1IHp6b6uTblh1Mh_8ckRf7Db5BHmXUKeaL9vDc-c33DkVyuUAUW0Xe9jtzUkGp5zhvSQ/s1600/20141009_112351.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh5ZAzhZMxlCkP6z_UY8KaJATx5yNBTRTCkZFGzgp_zquKxwQ3BWBhIWkYLXO_uM3vMtMGQiNM1IHp6b6uTblh1Mh_8ckRf7Db5BHmXUKeaL9vDc-c33DkVyuUAUW0Xe9jtzUkGp5zhvSQ/s1600/20141009_112351.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">You might even consider doing your own "future investigation" on whether yoga is something that might be beneficial for you, remembering to follow the appropriate precautions.</td></tr>
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In conclusion, Russell reported that in this phase 1 feasibility study, yoga improved posture, chest wall excursion, lower extremity muscle performance, and the self-reported body/image perceptions. </div>
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In my opinion, exercise is an extremely underutilized tool to improve health outcomes for CF patients...and basically everyone else (in the U.S., at least!). While we don't have a ton of evidence from a large scale study on the benefits of yoga specifically, there is PLENTY of evidence regarding the benefits of regular exercise. Maybe yoga doesn't sound so great to you...and that is OK! The best type of exercise will be something you enjoy, so that it will be done consistently. Since no new breakthrough therapies are hitting the market today...why not try EXERCISE as a natural, effective way to provide multiple health benefits? I know that when I recently attended a "restorative yoga" class with my friend Savannah, I left the class feeling awesome--both physically and mentally. I think that the attention paid to breath control in yoga makes it a particularly attractive option for patients with pulmonary dysfunction. </div>
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The next talk I want to summarize deals with a topic that some people wouldn't consider CF related at all, but I will argue that <b>mental health</b> issues can have deep and long lasting effects on health for both CF patients themselves, as well as their family members. As a CF mom, and a member of the Patient Engagement Advisory Committee for the CF Foundation, I've come to realize that mental health simply cannot be segregated from our physical health. Babies and young children are absolutely dependent on their parents for everything from proper nutrition to adherence to their prescribed CF treatment regimen. If a caregiver is struggling, negative effects can ripple throughout the family, and ultimately affect the child. When I was a new mother struggling with Brady's CF diagnosis, I would have never even considered bringing up my own mental health struggles with Brady's CF clinic team...even though I realize now that I probably should have. It didn't seem like the time or place for me to air my own concerns about how out of control I felt over my emotions, and life in general. Parents of children with special needs often put their own problems on the back burner, and find the topic to be too personal and painful to discuss. I struggled with depression, crippling anxiety in regard to clinic visits, and persistent sleep problems during Brady's infancy. I didn't want to admit that this time in my beautiful son's life was a really dark and scary period for me. I just figured that because CF sucks so much, I would probably never feel really good again, and that the depression and anxiety were par for the course. I'm sure that my struggle is not unique, and that many of you may potentially relate to the helpless state I found myself in. </div>
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<span style="font-size: large;"><i><b>What Healthcare Providers Need to Know About Postpartum Depression (Associated with Newborn Screening), But Were Afraid to Ask.</b></i></span></div>
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<span style="font-size: large;">Audrey Tluczek</span></div>
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This discussion dealt particularly with postpartum depression associated with a CF diagnosis following newborn screening. The speaker explained that she uses the term "postpartum depression" simply because it is defined by the onset of depression symptoms coinciding with the birth of a child. Unfortunately, for families with a newly diagnosed infant, that early period can be so overwhelming and scary. Many would probably consider postpartum depression/anxiety a problem exclusive to mothers--but when management of a chronic disease in a child is required, it can be just as pronounced in FATHERS, GRANDPARENTS, or anyone that is functioning as a care provider for the child. Tluczek discussed the need for more formal depression screening as a part of the regular clinic visit for families with newly diagnosed infants, and training of the clinic care team to provide useful interventions.</div>
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj2uMjiZMzoDulbfphKiZR7O2IvjkQ6tUPlHlonRp5vDLQSsaPT03dJMcdqovfYkT_lFYJNTiTRjVrDXv9IpDLG5VHF_HP43DrMyCsVEJqGCzaXH5hCCpDXjGLnhFo6AiUgccslRSNEOKg/s1600/20141009_113047.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj2uMjiZMzoDulbfphKiZR7O2IvjkQ6tUPlHlonRp5vDLQSsaPT03dJMcdqovfYkT_lFYJNTiTRjVrDXv9IpDLG5VHF_HP43DrMyCsVEJqGCzaXH5hCCpDXjGLnhFo6AiUgccslRSNEOKg/s1600/20141009_113047.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Clinic teams are becoming aware that mental health assessments NEED to become an integrated part of CF care. Unfortunately, many members of the care team may not be formally trained to recognize the symptoms.</td></tr>
</tbody></table>
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgq9rWosci1nqBcvOL3d3OiQoKyBQO5stDLAKRV3cq1s3mSnwNcg81S2M6U2SwBRnUJ5vWPTguhIDiZcObuHzX3urgsSDh127kiUVvFBBuP2vqdbC-g6z5PnSPdmZDU_ZDVBwGjuNW1h8o/s1600/20141009_113454.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgq9rWosci1nqBcvOL3d3OiQoKyBQO5stDLAKRV3cq1s3mSnwNcg81S2M6U2SwBRnUJ5vWPTguhIDiZcObuHzX3urgsSDh127kiUVvFBBuP2vqdbC-g6z5PnSPdmZDU_ZDVBwGjuNW1h8o/s1600/20141009_113454.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">For family members exhibiting signs of depression in association with care of the infant, treatment options can include psychotherapy, support groups, medication, and hospitalization for the most severe cases where the health of the individual or child is believed to be endangered.</td></tr>
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh3MkYSiD8f2Qyu0noBC88fxNziZ7m3MtrWd3gE1097dMwNdXSDjzG-uACnb-3IzV2otHQcwGapHL3egmsH3dKfdwEjUqKLCw78W7-bSW6D-_qBh1W-CyzJT8E9jSwS1sklm4DmpETuh4k/s1600/20141009_113546.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh3MkYSiD8f2Qyu0noBC88fxNziZ7m3MtrWd3gE1097dMwNdXSDjzG-uACnb-3IzV2otHQcwGapHL3egmsH3dKfdwEjUqKLCw78W7-bSW6D-_qBh1W-CyzJT8E9jSwS1sklm4DmpETuh4k/s1600/20141009_113546.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">This is important, because depression negatively impacts parent/child interaction.</td></tr>
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiutKvNXY7uHq59yB8_M93Yeufoql15yRnmm8aeqUOSiMmLXjn9FvwwAD42IUxtpxespYsiRbynJeblvcYsTgS5V3z2xaLYbdpdvbq43rD7cM73K0-z5G9hZZlyXJZRlT7I3p797LiKb04/s1600/20141009_113610.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiutKvNXY7uHq59yB8_M93Yeufoql15yRnmm8aeqUOSiMmLXjn9FvwwAD42IUxtpxespYsiRbynJeblvcYsTgS5V3z2xaLYbdpdvbq43rD7cM73K0-z5G9hZZlyXJZRlT7I3p797LiKb04/s1600/20141009_113610.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">I didn't realize how much my own mental health might be negatively affecting the precious child I wanted so desperately to protect.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjTftd58zGpxjFvShr8IP6-mdxwhYilIXJSl2XI5OyE6cTWcq2TWfGZl4PkMuIsTH0GeXf-Qt0XO3saVlkn-UNRJRpaZTVTT_WCuLR4qXMO3oEQfW2aRXF_OdTZnB4PIKRR5JeAJocm8oU/s1600/20141009_113628.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjTftd58zGpxjFvShr8IP6-mdxwhYilIXJSl2XI5OyE6cTWcq2TWfGZl4PkMuIsTH0GeXf-Qt0XO3saVlkn-UNRJRpaZTVTT_WCuLR4qXMO3oEQfW2aRXF_OdTZnB4PIKRR5JeAJocm8oU/s1600/20141009_113628.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Having a good relationship with a stable partner, family support, and the ability to provide for the basic social and economic needs of the family were found to be important factors in lessening the negative effects of post diagnosis depression. </td></tr>
</tbody></table>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj_ugxxR4dci-EU5nRy-Ghj5DHRTIuJF_i3lDNyNf2MJfZOaDFsDYOFFi_bdsHJ4GzAec61kCK7jQllqXWw9o7FFYLtDXxHAYNxsfeAbmXkCk-As1hFQmVtLQODxeZD6y5AvdK6i7TpP_8/s1600/20141009_113650.jpg" imageanchor="1" style="clear: right; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj_ugxxR4dci-EU5nRy-Ghj5DHRTIuJF_i3lDNyNf2MJfZOaDFsDYOFFi_bdsHJ4GzAec61kCK7jQllqXWw9o7FFYLtDXxHAYNxsfeAbmXkCk-As1hFQmVtLQODxeZD6y5AvdK6i7TpP_8/s1600/20141009_113650.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">The CF Foundation recommends that mental health screenings should be a part of the regular clinic experience for both CF patients, and their families. </td></tr>
</tbody></table>
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In this day and age of comprehensive care, I think it is so important that we feel that we can discuss depression, anxiety, OCD symptoms, or any mental health concerns with the CF care team. Looking back, I certainly wish I hadn't suffered in silence for so long. It is equally important that care teams are appropriately trained to recognize the symptoms of mental health issues, and provide options for treatment that may include referral to an outside professional. This topic is simply too important to remain taboo. It should be noted that while this talk focused specifically on postpartum depression, mental health concerns can come up at any time, especially with the demands of chronic disease management. These issues are important to address at any stage of life.</div>
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I know many of my readers tune in to the blog for science updates. I hope I haven't tarnished my rep by devoting this entire entry to the <i>fine art of living and thriving with CF</i>. Tomorrow, I plan to return to the cutting edge...and honestly, I need a night to sleep on the information I heard this morning in Symposium 8: <b>Gene Editing Strategies for Therapy and Research.</b> I believe that the future cure for EVERYONE with CF--regardless of their mutation, may become reality through one of techniques discussed in that room. Until tomorrow...</div>
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Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com2tag:blogger.com,1999:blog-7535774120903384819.post-91585058303001574982014-10-09T23:54:00.000-07:002014-10-09T23:54:02.321-07:00Updates from the NACFC--Thursday Oct. 9th, 2014<div class="MsoNormal">
I wait impatiently for the NACFC each year. This is my 4<sup>th</sup> year in attendance,
and I love having the opportunity to share the newest information with all of
you. This year, I flew to Georgia a few
days early, to spend some time with another CF family I have become close to
via social media through the last several years. As you know, CF is an isolating disease…and I
typically take every chance I get to make that real life contact. BE WARNED—if you invite me to visit—I might
actually do it! Thank you to Teresa,
Savannah, and Sam, who spoiled me with the finest in Southern hospitality, and
will have a permanent place in my heart.
<o:p></o:p></div>
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Teresa and I drove from Savannah to Atlanta on Wednesday
afternoon, retrieved our registration bag o’ goodies, and began networking with
the arriving attendees at the preferred meeting space—i.e., the bar. I can’t tell you how good it feels,
to be surrounded by so many brilliant professionals from around the globe working to cure CF. For me, the NACFC not
only expands my knowledge, it also expands my heart.<o:p></o:p></div>
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If you follow CF research, you are likely aware that Vertex
published <a href="http://investors.vrtx.com/releasedetail.cfm?ReleaseID=856185">data</a> from their phase 3 clinical trial of a VX-770/VX-809 combination
therapy for homozygous DF508 patients several months ago. The results from the study showed <i>modest </i>benefits in lung function and small decreases in sweat
chloride levels. To be honest, after the
FANTASTIC results experienced by most G551D/gating mutations with Kalydeco
alone—the results from the combo trial (while positive) were disappointing to
some. Vertex reports that they plan to
apply to the FDA with a new drug application in “the last quarter of this
year.” There has been plenty of
speculation on whether or not the FDA will consider the benefits of the
combination therapy statistically significant enough to approve the drug for
marketing. I am hopeful...but why haven’t we reached a greater level of improvement
with the combo for DF508? Theoretically,
an increase in CFTR protein trafficking to the cell surface (via the corrector
action of VX-809), plus an improvement in chloride channel open probability
(via the potentiator action of VX-770) should produce a more robust improvement. Dr. Deborah Cholon thinks her data can
help provide an explanation for the “smaller than hoped for” treatment effect
seen with the combination of these two molecules.</div>
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<o:p></o:p></div>
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<b><i><span style="font-size: 14.0pt; line-height: 115%;"><br /></span></i></b></div>
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<b><i><span style="font-size: 14.0pt; line-height: 115%;">Potentiator VX-770
Abrogates Pharmacological Correction by Destabilizing VX-809 or VX-661 Rescued
DF508 in Airway Epithelial Cells.<o:p></o:p></span></i></b></div>
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<span style="line-height: 115%;">First of
all, let’s review. The DF508 mutation
has several issues contributing to the overall protein dysfunction—<o:p></o:p></span></div>
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<span style="line-height: 115%;"><br /></span></div>
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<span style="line-height: 115%;">1) Decreased
stability in the folding mechanism of CFTR—resulting in decreased trafficking
to the cell surface<o:p></o:p></span></div>
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<span style="line-height: 115%;"><br /></span></div>
<div class="MsoNormal">
<span style="line-height: 115%;">2) Gating
defect for any protein that does manage to reach cell surface (similar to what
is seen with G551D) the channel doesn’t open and close properly—“rusty gate.”<o:p></o:p></span></div>
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<span style="line-height: 115%;"><br /></span></div>
<div class="MsoNormal">
<span style="line-height: 115%;">3) Increased
cell turnover at the cell surface (any protein that does successfully arrive in
the correct place in the cell, rapidly “unravels” and doesn’t actually become a
functional Chloride channel).<o:p></o:p></span></div>
<br />
<div class="MsoNormal">
<span style="line-height: 115%;">When researchers began exploring how to
correct CFTR function for DF508, they quickly realized that the road would not
be nearly as straightforward as it had been for the gating mutations. To achieve a robust amount of functional
CFTR, multiple problems must be overcome—requiring multiple compounds to get
there. Individually, both VX-770 and
VX-809 produce the desired action on lab cultured cell lines. Unfortunately, Dr. Cholon discovered that for
the DF508 mutation, chronic <b>exposure to VX-770 had a destabilizing effect </b>on
the amount of mature CFTR protein able to be “rescued” (successfully mature and
reach the cell surface). Furthermore, exposure to VX-770 also increased the rate of turnover (the unraveling process), ultimately reducing the amount of CFTR available for chloride transport. The higher the dosage of VX-770, the larger the destabilizing effect on DF508.</span><br />
</div>
<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgSu8EVyMAO-6Mc9nUGIPKU-WNVfJ8MtfRvmUvBSAsahyphenhyphenX7G2QGNN7CBWq09AKTMxMiNQgRBwg32qv-erNKwwarYq_DaQUYydQPBy6gbgYpvKqM3kqbUn01gdUD50omq5OJ9M6owlkSGMk/s1600/20141009_101901%5B1%5D.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgSu8EVyMAO-6Mc9nUGIPKU-WNVfJ8MtfRvmUvBSAsahyphenhyphenX7G2QGNN7CBWq09AKTMxMiNQgRBwg32qv-erNKwwarYq_DaQUYydQPBy6gbgYpvKqM3kqbUn01gdUD50omq5OJ9M6owlkSGMk/s1600/20141009_101901%5B1%5D.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Exposure to VX-770 reduces CFTR rescue (maturation)</td></tr>
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgEA3GSgdJmdVcK4Q07Gh222LxNoaJ6SnpDOHiZKYkm7hRPDLZW-wTQdMP7iPGBuR56V2wIrb2gUoYs7PHgZduyZgqO3KO_f5Gs_i0Y9aM7Xre971Gi046E0-CA_kpifxPLKMp0Zv1HN5c/s1600/20141009_102009%5B1%5D.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgEA3GSgdJmdVcK4Q07Gh222LxNoaJ6SnpDOHiZKYkm7hRPDLZW-wTQdMP7iPGBuR56V2wIrb2gUoYs7PHgZduyZgqO3KO_f5Gs_i0Y9aM7Xre971Gi046E0-CA_kpifxPLKMp0Zv1HN5c/s1600/20141009_102009%5B1%5D.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Also reduces the stability of the protein--leading to premature unraveling.</td></tr>
</tbody></table>
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgqDSmaIBeCvcovzk88jX3EJOK6yiYzlnmQYkHyU_lrYZ93E81AVyLVCHaPMOjxro8sLzn42qdceLy8vWn7WAgJYYy61laFF1behaItRyfUHvZUVqo6B0Yw6xkwH4PDpzijqEo89Mitco0/s1600/20141009_102119%5B1%5D.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgqDSmaIBeCvcovzk88jX3EJOK6yiYzlnmQYkHyU_lrYZ93E81AVyLVCHaPMOjxro8sLzn42qdceLy8vWn7WAgJYYy61laFF1behaItRyfUHvZUVqo6B0Yw6xkwH4PDpzijqEo89Mitco0/s1600/20141009_102119%5B1%5D.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">The negative effect of VX-770 exposure on DF508 was also observed in combination with the other corrector compound in development at Vertex--VX-661.</td></tr>
</tbody></table>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjs1yrnw7hAqUQPzoHiBmXyn-ex6wDHRPz6jYR7BDGJvw149rGjKPzxatOQd_am4zYzL1cj_OEuim8kv6OlTk4ywtLTsP-yWJ4ysMuWD0RWwChXzR722mnV4SHg6QsruXLbbQM0gNEFoR4/s1600/20141009_102243+(2).jpg" imageanchor="1"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjs1yrnw7hAqUQPzoHiBmXyn-ex6wDHRPz6jYR7BDGJvw149rGjKPzxatOQd_am4zYzL1cj_OEuim8kv6OlTk4ywtLTsP-yWJ4ysMuWD0RWwChXzR722mnV4SHg6QsruXLbbQM0gNEFoR4/s1600/20141009_102243+(2).jpg" height="360" width="640" /></a></div>
<br />
Researchers have been focused on finding a great corrector compound for DF508, but what they didn't realize is that "one size does not fit all" when it comes to potentiator action. VX-770 works great for gating mutations, but "disagrees" to a certain extent with DF508.<br />
<br />
Even with this crappy news--the fact remains that an overall positive treatment effect was still observed in the combo trial:<br />
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjyvsspJ9wW-DkwWREzBgMWe9kptJgV1OixTC8fnTiWdxaA2JRB0FGbDU9rm5NPXA2ci3Rw5flrytUzSiVP3QGA-muaeIwkeFvcXPy4vCTMDvdaGv3KBnXqPCw06f8SYeVLZEUVUcVI3cU/s1600/20141009_172628.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjyvsspJ9wW-DkwWREzBgMWe9kptJgV1OixTC8fnTiWdxaA2JRB0FGbDU9rm5NPXA2ci3Rw5flrytUzSiVP3QGA-muaeIwkeFvcXPy4vCTMDvdaGv3KBnXqPCw06f8SYeVLZEUVUcVI3cU/s1600/20141009_172628.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Relative improvement of 4.8% in FEV1 with combo treatment</td></tr>
</tbody></table>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhGPpcGS1etlEK7c1z5h8JQ7HW3cgI7Uwf_KwMl1fDeZs2VgivjJDN0UomX2pZax-A4bCF0rj4ukAclmQS0e_W3GLiUbsCPpTs0j60lxaojI6pG35JSRoUYDUD_sJicycZmo4uvwqYLY5E/s1600/20141009_172823.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhGPpcGS1etlEK7c1z5h8JQ7HW3cgI7Uwf_KwMl1fDeZs2VgivjJDN0UomX2pZax-A4bCF0rj4ukAclmQS0e_W3GLiUbsCPpTs0j60lxaojI6pG35JSRoUYDUD_sJicycZmo4uvwqYLY5E/s1600/20141009_172823.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Decreased rate of hospitalizations and IV antibiotic use with use of combo treatment for homozygotes.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiXo8x93-jVeS7C-nZbIh11k42HBJOkghPwVO3hZ1b_5VlLlh2g9mSfp2nqvyYC6dMfSZx_TwIdRNu_OO6OKsqhCNL3Z7h3z2rN3YYzE_L9Luutp6jeqokbwryqdsEaLxU_W7UKk5Pt9R0/s1600/20141009_172737.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiXo8x93-jVeS7C-nZbIh11k42HBJOkghPwVO3hZ1b_5VlLlh2g9mSfp2nqvyYC6dMfSZx_TwIdRNu_OO6OKsqhCNL3Z7h3z2rN3YYzE_L9Luutp6jeqokbwryqdsEaLxU_W7UKk5Pt9R0/s1600/20141009_172737.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Fewer exacerbations observed in trial group treated with combo therapy.</td></tr>
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I believe that Dr. Cholon's research does indeed provide some valuable insight into the smaller treatment effect seen in the combo trial. I think there there is still a decent chance for FDA approval of this combo therapy, but the hunt for a more suitable potentiator for DF508 is certainly ON. In the Q and A portion of this talk, Dr. Cholon described that while VX-770 may act negatively on the maturation and stability of CFTR, the molecule may still provide "alternate benefits" such as the improved regulation of bicarb (which can help normalize pH in airways--increasing the lung's own innate killing power of invading organisms), and subsequent reduction of the "bacterial load" in the lungs.<br />
<br />
I hate to report this as my first piece of Conference news, but there were several talks today, including an entire afternoon symposium session, focused on the negative effect of VX-770 on DF508 this year, and I'm not good at sugar-coating (Other titles along the same lines presented this afternoon:<br />
<i><br /></i>
<i>Potentiator Ivacaftor Abrogates Pharmacological Correction of DF508 CFTR</i>--Gentzsch,<br />
<i><br /></i>
<i>Mechanisms of Potentiator Inhibition of DF508 CFTR</i>--Bridges, <i>Opposing Effect of the VX-770 </i><br />
<i><br /></i>
<i>Gating Potentiator on the Corrected DF508 CFTR Function and Processing</i>--Lukacs. <br />
<br />
This info is certainly NOT what I wanted to hear or report, but it is also NOT A REASON TO FREAK OUT. The results of the combo trial were published months ago, and showed that the treatment effects of the combo were not as robust as we had hoped. At least now we have some idea WHY that is happening.<br />
<br />
Moving on...<br />
<br />
I didn't have to wait long for more positive news. Later in the same workshop this morning, we heard from R. Fitzpatrick from The Flatley Discovery Lab (a privately funded research facility dedicated exclusively to finding new potentiator and corrector compounds). <br />
<br />
<i><b><span style="font-size: large;">Progress Toward a CFTR Modulator System</span></b></i><br />
<br />
The Flatley Lab has high-throughput screening capabilities, and has tested over a million individual compounds, and more than 36,000 novel compounds for ability to positively affect CFTR rescue and open channel probability. Their research has already yielded several potential drug candidates. <br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgXpXoHl2Aim6tlJ81qi1IwTYsUKyLyr7wgRdavwBm8qhQPXE61YHIgdkFE724W9ixis19as9Yi1cHD388d9JwrzVQ0xNxmOPXFMPPf7fSDevSt7_3sclaAol7IK9IQUZ5DB4brnAhW-ig/s1600/20141009_105054.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgXpXoHl2Aim6tlJ81qi1IwTYsUKyLyr7wgRdavwBm8qhQPXE61YHIgdkFE724W9ixis19as9Yi1cHD388d9JwrzVQ0xNxmOPXFMPPf7fSDevSt7_3sclaAol7IK9IQUZ5DB4brnAhW-ig/s1600/20141009_105054.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Potential compounds for development. </td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg7fe9LPuj9rgSlRxElgDnkWAOC4DJIXAaBWKQfi9WByaiNbPwMUSH4l7HaYeA9_f90gvsVT2odBEcis3GujqyuVyWnQLauoGzvA9cuVsO9TdQ4xjV4Sqc_Br7_DBh8knXux0grB6ts4A8/s1600/20141009_105144.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg7fe9LPuj9rgSlRxElgDnkWAOC4DJIXAaBWKQfi9WByaiNbPwMUSH4l7HaYeA9_f90gvsVT2odBEcis3GujqyuVyWnQLauoGzvA9cuVsO9TdQ4xjV4Sqc_Br7_DBh8knXux0grB6ts4A8/s1600/20141009_105144.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Flatley Labs has found a compound with similar action to VX-809 called FDL169</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhVtWBskbqlxRjGMqdh5HYhpXG6OczzRnQEVXHvL9tCMDwfe4dV4a0MzwHioPCiN__KQwQ4IE-rMj2fAkpxKhXhE97Wr6bX7d359hWON9E2gGRVFyqT4GWGuBmRaJxTMmytShmdOK3e8AY/s1600/20141009_105320.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhVtWBskbqlxRjGMqdh5HYhpXG6OczzRnQEVXHvL9tCMDwfe4dV4a0MzwHioPCiN__KQwQ4IE-rMj2fAkpxKhXhE97Wr6bX7d359hWON9E2gGRVFyqT4GWGuBmRaJxTMmytShmdOK3e8AY/s1600/20141009_105320.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">And they are moving forward with development.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjj6hHZg5oP935qzdCR03KWak63hact_oDGlHidjCvTJp41ZuUuKfIGbPV5wtSBmgtSmg8IyzI4pkA_eaS26_xGd3JOMB_R-6EUlF56omoKUJW5cFbJKWN4BT9QC5nbl_YOATQAy0-zPas/s1600/20141009_105348.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjj6hHZg5oP935qzdCR03KWak63hact_oDGlHidjCvTJp41ZuUuKfIGbPV5wtSBmgtSmg8IyzI4pkA_eaS26_xGd3JOMB_R-6EUlF56omoKUJW5cFbJKWN4BT9QC5nbl_YOATQAy0-zPas/s1600/20141009_105348.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">They have also discovered several new potentiator candidates, that could be utilized in a future novel combination therapy. You may notice that the potentiators shown on this graph don't quite reach the level of benefit that is seen for VX-770 for G551D, but they may still prove superior to VX-770 if the DESTABILIZING effect described earlier on DF508 can be avoided. </td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhelLafKvCbNi8XxEUQhE8yqdSUQHypuiIUHWUwlOwLRzp06fW2HeX2kaaty8q8T_G0FahfS2wGi7EmjfRuSfArkuRk_OpSGhcQmQP35ZhiADqZ-YyMsCoRjd0XwSNV88_0tGaDr5TObyw/s1600/20141009_105504.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhelLafKvCbNi8XxEUQhE8yqdSUQHypuiIUHWUwlOwLRzp06fW2HeX2kaaty8q8T_G0FahfS2wGi7EmjfRuSfArkuRk_OpSGhcQmQP35ZhiADqZ-YyMsCoRjd0XwSNV88_0tGaDr5TObyw/s1600/20141009_105504.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Sorry this is so hard to read! The slide shows that Flatley Labs favored potentiator compound--FD2033129, does NOT inhibit CFTR correction in DF508. This is reason to believe that it may be a more feasible molecule for use in combination with a corrector for DF508.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjvdCR9_ODRoHgjgN1ssAiZ-NAjbZEVEcz1lkkZAapEej0v77_lOHOgqIIIIAHQK2nopg0IfxwAeo7xsFDNS3bXOJOBVam3xWmdAExY2_sbylJN8jPqb5opKhTAGFCNTMJO0CTfv54gfLM/s1600/20141009_105824.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjvdCR9_ODRoHgjgN1ssAiZ-NAjbZEVEcz1lkkZAapEej0v77_lOHOgqIIIIAHQK2nopg0IfxwAeo7xsFDNS3bXOJOBVam3xWmdAExY2_sbylJN8jPqb5opKhTAGFCNTMJO0CTfv54gfLM/s1600/20141009_105824.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Flatley Discovery Labs is hoping to initiate trials on some of their discovered compounds in "December of this year, or January of next." They are already discussing combining multiple correctors with their novel potentiator candidate to create a "second generation" combo therapy for DF508.</td></tr>
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The last talk I want to summarize in this entry was given by Fred Van Goor from Vertex:<br />
<br />
<i><b><span style="font-size: large;">R117H is a Residual Function Mutation That Is Potentiated by Ivacaftor</span></b></i><br />
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As you may know, R117H is a mutation where the CFTR protein is observed at the cell surface, and SHOULD be effectively potentiated by Kalydeco. In trials, Kalydeco was found to have a "less statistically significant treatment effect" for this group, and R117H was subsequently excluded from the FDA's expansion of approved mutations earlier this year. Van Goor proposes that the smaller effect observed in R117H as compared to other gating mutations is NOT a consequence of diminished action of Kalydeco, but rather, a function of the milder nature of the R117H mutation itself. <br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgjmjlK1lb12x98Knq-rPmxvWYHmzH7VPMUNf5GMjmxy0PjMcFR7HysReChdWjkPOKg78FAjnUMi4xaxGihMEr_PtfEyL8Lv9v7_Vsp2yVoSG1aPY0pcklzTVGDtXHRkCQRd7cBS0-X-Hw/s1600/20141009_103359.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgjmjlK1lb12x98Knq-rPmxvWYHmzH7VPMUNf5GMjmxy0PjMcFR7HysReChdWjkPOKg78FAjnUMi4xaxGihMEr_PtfEyL8Lv9v7_Vsp2yVoSG1aPY0pcklzTVGDtXHRkCQRd7cBS0-X-Hw/s1600/20141009_103359.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">R117H is generally considered a "milder" mutation. Many patients with this mutation are pancreatic sufficient. Serious lung dysfunction often doesn't present until later in life within this group, and I know of several patients with this mutation that weren't even diagnosed until adulthood. </td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgQEgE0uRjYFFlKSsczI7pszhkjoBkctxY7yQ3O4-zOngSkWrxbO1mXn6pZA5Jr8tH7SCO7vixahHqYKuLw4tg_707hiNY7QFcysy1geuhRcoi8mcbCVYCjwTRgBpPHJTveIXo4dYwn8Yc/s1600/20141009_103555.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgQEgE0uRjYFFlKSsczI7pszhkjoBkctxY7yQ3O4-zOngSkWrxbO1mXn6pZA5Jr8tH7SCO7vixahHqYKuLw4tg_707hiNY7QFcysy1geuhRcoi8mcbCVYCjwTRgBpPHJTveIXo4dYwn8Yc/s1600/20141009_103555.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Patch-clamp studies show that Ivacaftor increases the frequency of channel opening of the CFTR protein at the cell surface for the R117H mutation.</td></tr>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjSw5N9mxyzBT-2nLIj4uEnXGp8YJbDsyanhHPepUAFM2_FF-jlxJigzGcKN8OkwzIkgDQwhvEA8uWTzTf7eJ8owml3_WdrGHQtKeacOqHUxCL0JCe0WZVfys75XxJYoMmO6kkktiZHfO4/s1600/20141009_103621.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjSw5N9mxyzBT-2nLIj4uEnXGp8YJbDsyanhHPepUAFM2_FF-jlxJigzGcKN8OkwzIkgDQwhvEA8uWTzTf7eJ8owml3_WdrGHQtKeacOqHUxCL0JCe0WZVfys75XxJYoMmO6kkktiZHfO4/s1600/20141009_103621.jpg" height="360" width="640" /></a></div>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjJP3BsLJa4jyvsGwdpmP8eOFnv6evGM1xHgVXQspPMbs0mfn6s_QYK1LvdEEw83Q32uxHYIzvXPA7NFve0fUcI9LoYX2EN97gTkTqPDsGIgb63U_zcZmXwaHqaZ1EjS9W2HJ3X40jtPTs/s1600/20141009_103912.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjJP3BsLJa4jyvsGwdpmP8eOFnv6evGM1xHgVXQspPMbs0mfn6s_QYK1LvdEEw83Q32uxHYIzvXPA7NFve0fUcI9LoYX2EN97gTkTqPDsGIgb63U_zcZmXwaHqaZ1EjS9W2HJ3X40jtPTs/s1600/20141009_103912.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Van Goor went on to show that treatment benefit to R117H could be increased by the addition of Lumacaftor (VX-809)</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiLRJJXkOfNShdUHgi4hcgpjUTXeEZ2l9qKpNrXwe_uJywhhVWjpHhE0YRVZ8bQqAe6TB4Sm9nmd43Dny13BbjImd8x-vJKfLAx_Lsr6l8te0FVdidMVyowu7hkDs_8qJRvif0UnNjREdQ/s1600/20141009_104212.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiLRJJXkOfNShdUHgi4hcgpjUTXeEZ2l9qKpNrXwe_uJywhhVWjpHhE0YRVZ8bQqAe6TB4Sm9nmd43Dny13BbjImd8x-vJKfLAx_Lsr6l8te0FVdidMVyowu7hkDs_8qJRvif0UnNjREdQ/s1600/20141009_104212.jpg" height="360" width="640" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">All signs indicate that R117H is a good candidate for both Kalydeco monotherapy, as well as combination therapy.</td></tr>
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If Kalydeco is working so well for R117H, then why were smaller improvements in FEV1 observed in clinical trials? Van Goor suspects that this group was unable to achieve the massive gains in lung function observed in the other gating mutations, simply because the lung function of patients in this group was already very good to begin with. You can't gain 10% lung function if it has never been lost in the first place. To further illustrate this point, let's consider my son Brady's response to Kalydeco. Brady has DF508 and G551D, and I have written VOLUMES about the benefits we have observed in him: disappearance of serious sinus polyps, huge drop in sweat chloride levels, increased energy, increased BMI and nutritional status, etc... BUT, Brady did NOT see a huge improvement in lung function because his lung function was good to begin with. The absence of a huge improvement in FEV1 DOES NOT mean that the drug is not working incredibly well. You can't keep going up if you are already near the top! Based on the evidence presented today, and over the last several years, I agree whole-heartedly with Van Goor's explanation. According to the <a href="http://investors.vrtx.com/releasedetail.cfm?ReleaseID=875448">press release</a> published by Vertex today,<br />
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<span style="background-color: white; color: #665f58; font-family: Verdana, Tahoma, 'DejaVu Sans', sans-serif; font-size: 12px; line-height: 18px;">"<i>Based on the Phase 3 data, Vertex submitted an sNDA in the U.S. and MAA variation in </i></span><i><location idsrc="xmltag.org" style="background-color: white; color: #665f58; font-family: Verdana, Tahoma, 'DejaVu Sans', sans-serif; font-size: 12px; line-height: 18px;" value="LR/eur">Europe</location><span style="background-color: white; color: #665f58; font-family: Verdana, Tahoma, 'DejaVu Sans', sans-serif; font-size: 12px; line-height: 18px;"> for approval of ivacaftor in people with the R117H mutation. Vertex's sNDA for the use of ivacaftor in people with the R117H mutation will be the subject of an FDA Advisory Committee Meeting of the Pulmonary-Allergy Drugs Division on </span><chron style="background-color: white; color: #665f58; font-family: Verdana, Tahoma, 'DejaVu Sans', sans-serif; font-size: 12px; line-height: 18px;">October 21, 2014</chron><span style="background-color: white; color: #665f58; font-family: Verdana, Tahoma, 'DejaVu Sans', sans-serif; font-size: 12px; line-height: 18px;">. In </span><location idsrc="xmltag.org" style="background-color: white; color: #665f58; font-family: Verdana, Tahoma, 'DejaVu Sans', sans-serif; font-size: 12px; line-height: 18px; margin-bottom: 0px !important;" value="LC/us">the United States</location></i><span style="background-color: white; color: #665f58; font-family: Verdana, Tahoma, 'DejaVu Sans', sans-serif; font-size: 12px; line-height: 18px;"><i>, Vertex is seeking approval of ivacaftor in people ages 6 and older with the R117H mutation</i>."</span><br />
<br />
I am very hopeful that we will see an approval for R117H soon. There is so much more to say, but it is time to sleep so I can do it all again in a few hours! Tune in tomorrow for news about:<br />
<br />
<i style="font-weight: bold;">The Relationship Between Exercise Capacity and Glucose Tolerance in a Pediatric CF Population Not Diagnosed with CF-related Diabetes--</i>Karla Foster<br />
<br />
<i style="font-weight: bold;">Yoga Improves Posture and Muscular Performance In Adult Persons with Cystic Fibrosis--</i>Scott Russell<br />
<br />
<b style="font-style: italic;">What Healthcare Providers Need to Know About Postpartum Depression (associated with Newborn Screening) But Were Afraid to Ask--</b>Audrey Tluczek<br />
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Plus, news from an amazing Plenary Session and much much more! As always, please forgive my typos. These events involve wine...<br />
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Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com4tag:blogger.com,1999:blog-7535774120903384819.post-68103482416854462762014-07-29T18:34:00.000-07:002014-07-31T08:30:11.264-07:00Conflict Free ZoneI do not have ANY AFFILIATIONS that I need to disclose. I am not employed by anyone. I hold several volunteer positions within The Cystic Fibrosis Foundation (Great Strides Spokane, WA Chair, Idaho State Advocacy Chair, Patient Engagement Advisory Committee member). I have zero conflicts of interest. In fact, my only real interest in this topic is to see my child, and others that need it, have access to Kalydeco and other new therapies that might be available soon to treat CF. This entry is simply the way that I see the flood of recent media attention, as a parent of a child with CF. Brady has been taking Kalydeco since February 10, 2012.<br />
<br />
I can feel the storm brewing as Vertex's VX-809/VX-770 combo approaches the doors of the FDA. Kalydeco, The CF Foundation, and the astronomical price of this little blue pill have also been very hot topics in economic, pharmaceutical, and medical journals lately. Bloggers all have their own point of view on the issue. I think I know a lot about it, so I'm offering mine--<br />
<br />
<b><span style="font-size: large;">The Issue--The Price of Kalydeco.</span></b><br />
First of all, let me say that Brady has been enrolled in the Vertex GPS (patient assistance program), since his 6th birthday. The case managers at Vertex have been really phenomenal to work with. They are total experts at getting things done with insurance. Nothing but good things to say about this program. The tricky part is that you must fall under the FDA approved guidelines to qualify for this program. We pay $15/month out-of-pocket for Kalydeco. Seems too good to be true. Before Brady turned 6, Kalydeco was covered by the private insurance (Blue Cross/Blue Shield of Idaho), that we have through my husband's employer (Yes, we got insurance coverage, "<a href="http://luckycfmom.blogspot.com/2012/02/hiking-off-label.html">off-label</a>" for Brady at age 4 1/2.). Even though the approved label has now been expanded to several other gating mutations, and patients in other countries, the price of Kalydeco has mysteriously climbed over $6K/month over the last 2 1/2 years. Why is that? According to Vertex, they set the price of Kalydeco based on "<i>the perceived benefit for the limited patient population</i>." Shouldn't MORE patients lead to a LOWER price? Ha! Not in a market economy!<br />
<br />
The truth is that Vertex, as a company, took a huge blow with the recent failure of their hepatitis drug Incivek. When Incivek was approved by the FDA in 2011, it generated huge sales for Vertex--estimated at around $951 million for the first 6 months it was on the market. Their sales came to a screeching halt, as Abbvie and Gilead came out with newer, superior Hepatitis drugs, making Incivek virtually obsolete. This <a href="http://www.forbes.com/sites/johnlamattina/2013/11/04/vertex-failure-shows-biotech-is-not-immune-to-big-pharma-type-layoffs/">Forbes</a> article discusses the financial impact on this failed Hep C drug, which prompted Vertex to cut 15% of their workforce. The article describes how "<i>This has created an enormous gap in future earnings and Vertex needed to cut costs to make up for this loss</i>." <br />
<br />
Vertex is a FOR-PROFIT company in a free market economy. They want to remain profitable as a business, so they can keep their doors open. Vertex is using the sale of Kalydeco--their one and only successful drug, to make up for their losses in other areas of research, and close the expected earnings gap.<br />
<br />
<span style="font-size: large;"><b>How Can Vertex Do That? </b></span><br />
<span style="font-size: large;"><b>Why Doesn't The CFF Make Them Charge Less?</b></span><br />
<br />
Vertex has set the price of Kalyeco so extremely high, that it has delayed access to the drug in some countries (Australia and Canada most notably) and caused push-back from <a href="http://online.wsj.com/articles/costly-drug-vertex-is-denied-and-medicaid-patients-sue-1405564205">Medicaid in Arkansas</a>. Lately, I have been reading some criticism on the role of the CFF in this mess, and it upsets me. This is what I know. <br />
The Cystic Fibrosis Foundation has invested millions of dollars into Vertex (formerly Aurora Biosciences). This money has been used mainly to set up and operate a high-throughput screening lab, to allow scientists to screen thousands of compounds in search of those with the ability to restore chloride channel function. When compounds are discovered that enhance chloride channel activity, they can then be tweaked and further devoloped, tested on human cell lines in the lab, and eventually progress toward clinical trials in humans. That is exactly how Kalydeco was discovered. The work done by Vertex with the money invested by The CFF has been nothing short of incredible. This is the cutting edge of genetic science. Our understanding of CFTR function has been enriched enormously by their work, which has really set the stage for the whole "small molecule treatment based on mutation class" era that we are entering today. Even if Vertex hadn't uncovered a blockbuster compound like Kalydeco...<i>we still would have gotten our money's worth.</i> They did EXACTLY what they were given money to do, and they did a damn good job. Never in the negotiation did The Cystic Fibrosis Foundation have the power to demand where Vertex must set the price of a drug--if it were to be discovered. The CFF hoped they would find ANYTHING at all...and they found Kalydeco. Amazing! At that point in time, the CFF was knocking on doors begging pharmaceutical companies to do any CF research at all. We didn't hold the power, or the stock, to have any real sway in setting the price point for Kalydeco. That isn't how the free market operates. Honestly, investing in research, there are MANY more failed projects than success stories. The CFF has put millions of dollars into numerous companies over the years to do research that resulted in absolutely nothing. That seriously happens all the time! Sometimes all we learn from our investments is what DOESN'T WORK. Of course, some of those research risks also led to drugs like Pulmozyme, Tobi, and Cayston. Ahhhh science--strikes and gutters. We paid Vertex to do the research so that it might not take their company out of business if they happened to roll a gutterball with their CF research. Instead, they rolled a strike by discovering Kalydeco. <br />
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The money invested by The CFF into Vertex served to take away some of the huge financial risk of entering the realm of CF research. Without development incentives, companies wouldn't bother getting involved at all. The CF population is very small, and it is much more PROFITABLE to be involved in research for a cancer, diabetes, or cholesterol medication--that could potentially be prescribed to MILLIONS of people rather than a few thousand. The fact that we are having this conversation means that the miracle drug exists...and falls into the "good problem to have" category, as far as I am concerned.<br />
<br />
<span style="font-size: large;"><b>The Unfair Part</b></span><br />
<br />
The major problem I have with the way this has played out, is that access discrepancies leave some CF families PAYING TWICE. The CF Foundation funded a significant portion of the the cost to develop Kalydeco, and the CF community works hard to keep money flowing to The CFF, through grassroots fundraising. CFF execs also work hard to bring in millions in major donations. It just feels wrong and dirty that the price of Kalydeco is so exorbitantly high, that some eligible patients may never get the chance to try it. In the words of Dr. Francis Collins, "<a href="http://www.jsonline.com/watchdog/watchdogreports/charitys-investment-a-prescription-for-profits-for-drug-maker-p79tfc9-208027961.html">Drugs that are lifesaving, ought to be affordable</a>." It makes me so sick to think about the patients in Australia, and other parts of the world that could benefit from Kalydeco, but don't have access to it because of cost negotiations. After all, it isn't the CF community's fault that Vertex's Hep C drug failed! Why are we being saddled with the burden of recouping totally unrelated losses? Because that is the way business works. Vertex charges $300K/yr for Kalydeco simply because THEY CAN. I obviously have some mixed feelings about Vertex. <br />
<i><br /></i>
<i><b>The Good</b></i>--The scientists couldn't be any higher on a pedestal in my mind...<br />
<i><b>The Bad</b></i>--but I have issues with some of the executive behavior.<br />
<i><b>The Ugly</b></i>--Vertex execs have made multi-millions on questionable stock exchanges, and are being investigated by the SEC. Some patients that desperately need the drug, still don't have it, because of price issues.<br />
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<b><span style="font-size: large;">Rumors About "Conflicts of Interest" for The CFF</span></b><br />
<br />
The Cystic Fibrosis Foundation owns a small % of the rights to Kalydeco and receives royalties on its sale. The money that comes in from royalties is re-invested in further scientific research. The CFF invested $75 million in Vertex to develop Kalydeco. The CFF then sold a portion of those rights for $150 million (double our original investment!), investing that money in further projects with Vertex, and new projects with pharma giants Pfizer and Genzyme. Some people argue that it is unethical for The CFF to promote the sale of Kalydeco, which it now considers the standard of treatment for approved mutations, and receive cash royalties for every astronomically priced prescription that is filled. This is an investment model that The CF Foundation has used in the past, that has successfully generated millions for new research. In fact, $20 million of the original $75 million that was invested in Vertex came from the royalties that The CFF made from sales of TOBI. Was THAT wrong? And I will argue that The CFF recommends Kalydeco as a standard of treatment because the science shows it is by far the most beneficial treatment for these eligible CF patients--not to line their own pockets. It would be absurd if The CFF DIDN'T recommend Kalydeco! This is certainly not the first time The CFF has used royalties to further scientific discovery, and it has resulted in some amazing improvements to treating CF. This "venture philanthropy" model is precisely what sets The CFF apart from other disease non-profits. The CF Foundation may not have the power to demand that Vertex charge a lower price, but they can choose to broaden their investment portfolio, in hope of giving Vertex some direct competition. <span style="text-align: center;">In this article, Dr. Beall says,</span><br />
<br />
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"W<span style="background-color: white; color: #333333; font-family: 'Droid Serif'; font-size: 14px; line-height: 20px;">ithout the financial support of the foundation drugs such as Kalydeco would never get on the market".</span> <span style="background-color: white; color: #333333; font-family: 'Droid Serif'; font-size: 14px; line-height: 20px;">He rejected the idea of using the royalty money to help patients pay for the medical care, noting that foundation needed the money to entice large drug companies such as Pfizer to get involved in risky cystic fibrosis drug research. </span><span style="background-color: white; color: #333333; font-family: 'Droid Serif'; font-size: 14px; line-height: 20px;">He said he could only express his concern about the price and invest funds with other companies that might develop competing drugs that someday could bring the price down. </span></div>
<div style="text-align: center;">
<span style="background-color: white; color: #333333; font-family: 'Droid Serif'; font-size: 14px; line-height: 20px;"><a href="http://www.medpagetoday.com/Pulmonology/CysticFibrosis/39217">Cystic Fibrosis: Charity and Industry Partner for Profit</a></span></div>
<br />
Bringing competitor potentiators and correctors to the market is how we are going to influence the price of treating CF, and The CF Foundation has been absolutely masterful at <b>not</b> putting all their eggs in one basket. The CFF now has numerous partners like Pfizer, Abbvie, N30, and Galapagos working to bring better, competitive compounds to market. Vertex got burned when competitors made their Hep C drug Incivek obsolete...the same exact thing could happen to Kalydeco or the VX-809/VX-770 combo. The CF Foundation is working to lower the cost of these treatments in the most effective, realistic manner our system allows. And I honestly don't see the conflict of interest in re-investing a portion of the sale of Kalydeco back into research. As a parent, and "paying customer," I would rather see at least a small part of the monthly payment from our insurance go back to The CFF for continued research. I think that is the investment that will provide Brady with the greatest returns--in the form of a long healthy life. The alternative is to see 100% of the money go to Vertex, and miss out on those research opportunities. It isn't going to lower the price of Kalydeco a single penny if The CFF sells their rights. It would just be someone else collecting the check at the end of the day. You know how many Great Strides walks and family bake sales it would take to raise the $150 million in royalties we have received from Kalydeco? I say we keep the damn money and put it right back into the laboratory. <br />
<br />
<b><span style="font-size: large;">Speaking of Fat Checks...I've Heard Some Complaints About the Salaries of The CFF Executives Also. </span></b><br />
<br />
The CFF has been lead by CEO Dr. Bob Beall, and COO Rich Mattingly for well over 30 years. These men have dedicated their lives and careers to creating hope, where there was none. In terms of non-profit disease organizations, The Cystic Fibrosis Foundation is the envy of the industry. They have had more SUCCESS in changing the course of the history of a genetic disease than some people believed possible. That success came from a radical departure from the typical non-profit operations. That success came from huge risks that others weren't willing to take. That success came because our leaders are absolutely extraordinary. Charitywatch.org reports Dr. Beall's <a href="http://www.charitywatch.org/hottopics/Top25.html">salary</a> at slightly over $1 million per year. I believe that he is worth every single penny. We simply wouldn't be where we are today without their unique vision and <i>never quit</i> attitude. I am not interested in a mediocre leader for this organization. I want to cure this disease. Our leadership is NOT where we want to settle for second-rate, and try to pinch pennies. Just because it is a non-profit organization, doesn't mean that The CFF doesn't compensate it's own employees, and we want the best! Of course, there are thousands of individuals that contribute great value to the organization on a volunteer basis. The executive team, however, is made up of top notch professionals that have made curing CF their entire <b><i>career</i></b>. Criticize all you want, but the fact is, that Dr. Beall's salary is a mere drop in the bucket compared to the multi-millions he BRINGS IN to The CF Foundation every year. He secured $20 million from Bill Gates alone, in 1999, to get the initial project (The Aurora Project) with Vertex (formerly Aurora Pharmaceuticals) off the ground. I will argue, until I am blue in the face, that the CFF execs are a HUGE NET WIN for the CF Community. I admire them as heroes, and can't imagine trying to put an actual value on their worth. If we want the best in the business, we have to be willing to compensate them appropriately. And after 30+ years at the same organization, I can't imagine anyone accusing them of staying with CFF to get rich. INDUSTRY is where the big money is made with expertise like that. I stand in firm defense of The CFF execs, and their SUCCESSFUL venture philanthropy business model. If you take Kalydeco, Pulmozyme, Tobi, Cayston, prescription digestive enzymes, or basically any other drug developed to treat CF, you should thank Bob Beall, Rich Mattingly, and Preston Campbell at the CFF. They are responsible for extending people's lives. <br />
<br />
<span style="font-size: large;"><b>Back to the <i>Value</i> of Kalydeco </b></span><br />
<br />
Lastly, I've been reading plenty of speculation on the effectiveness of Kalydeco, mostly in financial papers. <br />
Is Kalydeco really THAT good? Is it really worth the price if patients don't experience close to a "cure"? What about the side effects? <br />
<br />
Here is the deal--just as no two cases of CF are alike (even with siblings with CF), no two patients will respond in exactly the same way to Kalydeco. One big factor is how much "permanent damage" or bronchiectasis, the patient has sustained. When a patient (with a gating mutation) begins taking Kalydeco,<br />
their Chloride transport is suddenly turned ON. This new found functioning at the cell surface causes a flush of hydration to those tissues and can stir up some mucous plugs and pockets of infection that may have been hanging out for DECADES in some patients. For most adults initiating Kalydeco, they go through a period of time that can last from several days to even a few months where their body sort of PURGES old mucous and adjusts to the new mode of operation. Stirring up these old infections can cause fever, flu-like symptoms, almost unbelievable amounts of flying mucous, and an overall feeling of unwellness (from what I've heard). HOWEVER, once the initial clearing phase is over, patients report deeper breathing, more watery mucous, and decreased coughing. In general, well-being is IMPROVED when the body's chloride is functioning more normally. <br />
<br />
<i>Imagine a 40 year old man that had smoked cigarettes daily since the age of 15. If he stopped smoking one day, his body would adjust, and he would experience some HUGE benefits to his breathing ability. His lungs would start to clear some of the gunk, and greatly slow the rate of decline of lung function. Still, he may have already developed some emphysema or COPD, and will never breath like someone who had never smoked a day in their life. He may still need medications to treat his lungs, and may still succumb to illnesses like pneumonia more easily. He may still, eventually die of lung related problems...even though he stopped smoking. </i><br />
<br />
Hopefully, we don't have many smokers in the CF community, but you can relate the huge spectrum of responses to Kalydeco to this scenario, and understand that the type of maintenance therapies required to manage each person's disease from that point forward will be completely unique. Scientists are learning more every year about how Kalydeco impacts the body, and have broadened their scope of interest beyond the lungs. They are looking at how Kalydeco impacts digestion, liver function, sinus function, development of CFRD, etc... I feel compelled to attend the NACFC each year to stay updated on the newest Kalydeco research. So far, the more I learn, the better it gets. Here are some of the highlights--<br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjrUetvx7BwTiY9VI7SJTEhcp60P_M9Pk_xDJrm4prtny8jGHCDukE3pEWPHkwKMcnsXKYv7D-hTPwBwDip7N0YvRMFCoz5yb81nvS8iFY3Jg3e8E4NYzAYK10M-DCZqzEwlfujJMpl87s/s1600/FEV.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjrUetvx7BwTiY9VI7SJTEhcp60P_M9Pk_xDJrm4prtny8jGHCDukE3pEWPHkwKMcnsXKYv7D-hTPwBwDip7N0YvRMFCoz5yb81nvS8iFY3Jg3e8E4NYzAYK10M-DCZqzEwlfujJMpl87s/s1600/FEV.jpg" height="225" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">You don't need to be a scientist to read this graph. I burst into tears the first time I saw it. Huge increase in FEV1% predicted almost immediately upon initiation of Kalydeco--maintained fairly evenly for the course of the trial.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjUv35FDI4uAPp68PjvP7GB9w84p9wN4i9tqnaJmDyDwvipXccDRgVqroTi-7_C9EzR_ywhA4tlrk8fNlVzFRfgVe_bzDwGodw5g9xbHXJnZ70oozQr5gyRCiFtsUGKecy3NemFtnTm6-U/s1600/sweat.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjUv35FDI4uAPp68PjvP7GB9w84p9wN4i9tqnaJmDyDwvipXccDRgVqroTi-7_C9EzR_ywhA4tlrk8fNlVzFRfgVe_bzDwGodw5g9xbHXJnZ70oozQr5gyRCiFtsUGKecy3NemFtnTm6-U/s1600/sweat.jpg" height="225" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Another clear example of the power of this drug. We have NEVER had anything in our hands with the power to change sweat chloride levels--which are (at least loosely) linked to CFTR function. This graph shows a huge decrease in sweat chloride for patients taking Kalydeco--again, sustained through the course of the trial.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgZJ3t0Y-ODzJGjwLmV811Nw48qIzPd8czAmatvCXwlPIaNZ0HT9CUg3MA_Fwml-N0vjxxMBw4-N-D9IJLXsrDcVf4oRhx0n_B1rsvNY68aiRE6dRTEvnqA0GBF_pcY2yhLfnGg4n73bYA/s1600/20131017_104836.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgZJ3t0Y-ODzJGjwLmV811Nw48qIzPd8czAmatvCXwlPIaNZ0HT9CUg3MA_Fwml-N0vjxxMBw4-N-D9IJLXsrDcVf4oRhx0n_B1rsvNY68aiRE6dRTEvnqA0GBF_pcY2yhLfnGg4n73bYA/s1600/20131017_104836.jpg" height="300" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">This is a summary from the GOAL study, which examined different study endpoints than were reported on in the phase 3 trial. Report represents longer term data...shows continued awesomeness. </td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgN30-XSOs0bdQESPF7qdMiTDCJjFWPkOIy2qajE1zdg9fHrSwwG2pE8MIFSt9Hor-hAMkQvf-Y1lXTUofU3O5zmgKEVnRCZXXaBO1e5aL6mFaOdY3G5BFnO7wdCJ1Fsr2Wcd-5gP0pqH8/s1600/20131017_104519.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgN30-XSOs0bdQESPF7qdMiTDCJjFWPkOIy2qajE1zdg9fHrSwwG2pE8MIFSt9Hor-hAMkQvf-Y1lXTUofU3O5zmgKEVnRCZXXaBO1e5aL6mFaOdY3G5BFnO7wdCJ1Fsr2Wcd-5gP0pqH8/s1600/20131017_104519.jpg" height="300" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">I saw data for the first time at The NACFC 2013 that patients experienced a decrease in hospitalization rate with Kalydeco.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgTIUknFbs_ulyb_0ub43HFI74HiB6vKC59irQfdVMMNKMxp71L3-IUpYiTdgnZqylrxTIPePcbEBMXqyHgvoNpKcUQpdNygmomUDQVH-Dwc6bbkqc07Tn_6yMDzzDuADYUn5enqMNrDxU/s1600/20131017_104727.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgTIUknFbs_ulyb_0ub43HFI74HiB6vKC59irQfdVMMNKMxp71L3-IUpYiTdgnZqylrxTIPePcbEBMXqyHgvoNpKcUQpdNygmomUDQVH-Dwc6bbkqc07Tn_6yMDzzDuADYUn5enqMNrDxU/s1600/20131017_104727.jpg" height="300" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Patients taking Kalydeco also have 35% reduced odds of culturing positive for Pseudomonas.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiKUfgJG2xgXlLJqZkAzmkOrGXy3w7D3SmNAesmXGtbPZZkBuZcwvCETT8f3mfiGrAYR8bWWpJBEJSXip6LeeAibsHgOp9RFSS4jBsevYaO9uNU1aprxYWufBAuRjdoD3b27YVY64-BEuk/s1600/20131017_175158.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiKUfgJG2xgXlLJqZkAzmkOrGXy3w7D3SmNAesmXGtbPZZkBuZcwvCETT8f3mfiGrAYR8bWWpJBEJSXip6LeeAibsHgOp9RFSS4jBsevYaO9uNU1aprxYWufBAuRjdoD3b27YVY64-BEuk/s1600/20131017_175158.jpg" height="300" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Ivacaftor has been shown to normalize the pH in the lung, enhancing the body's own natural lung defense--proper pH promotes the lungs own "killing power" of invading bacteria.</td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhcSrakCxYPQnIzJezNO-RIyTG892Jgz7cDYzNcd_Z36ZjZlNkLsHhC-iPCsFVdqyCJqWY9KTGKPk6wON1oDNtly8gF-BlQJPAri-l_ZxMxrXs-D1iZC2WJKfJsij4Lz4ULWg3Tk2Y_WDQ/s1600/20131017_180647.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhcSrakCxYPQnIzJezNO-RIyTG892Jgz7cDYzNcd_Z36ZjZlNkLsHhC-iPCsFVdqyCJqWY9KTGKPk6wON1oDNtly8gF-BlQJPAri-l_ZxMxrXs-D1iZC2WJKfJsij4Lz4ULWg3Tk2Y_WDQ/s1600/20131017_180647.jpg" height="300" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Ivacaftor has also been shown to normalize pH in the intestines, enhancing the function of the digestive enzyme replacements that most CF patients rely on at every meal. The enzymes are designed to dissolve when their environment turns from <i>acidic </i>to <i>basic</i>. This is supposed to happen at the beginning of the small bowel. CF patients often have trouble achieving that basic environment because of impaired bicarb channel function (bicarb "neutralizes" the acid, changing the pH in healthy individuals). Many CF patients take acid blockers of some kind to aid the body in achieving a basic intestinal pH. Patients taking Kalydeco saw intestinal pH normalize, thereby bringing their bodies into the zone where their enzymes would work at their absolute best. </td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhilxSb12n7bSEuabf4kCSM0OxijWictkMUZINeT3pImgPPzTctN0Mw74rZBcPxrTUYz8yhy_dfDsH7oEwEnAyMgF-m7RwU9TIzz-JcZUXZ9Z7lLuBVJEsF6WbKnQKcnK0M5V_rKQxJ19s/s1600/20131019_093834.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhilxSb12n7bSEuabf4kCSM0OxijWictkMUZINeT3pImgPPzTctN0Mw74rZBcPxrTUYz8yhy_dfDsH7oEwEnAyMgF-m7RwU9TIzz-JcZUXZ9Z7lLuBVJEsF6WbKnQKcnK0M5V_rKQxJ19s/s1600/20131019_093834.jpg" height="300" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">I am hoping to hear more information on Kalydeco's ability to impact pancreatic function and the development of CFRD at upcoming Conference! Still an unknown, but an exciting prospect! </td></tr>
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Beyond all this "official data," you can read the most recent update on <a href="http://luckycfmom.blogspot.com/2014/03/a-different-filter.html">Brady's personal response to Kalydeco</a> in this previous blog entry.<br />
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<b><i>Bottom line</i></b>: If you want to question the effectiveness of Kalydeco, please bring some real data to back it up. Published information, and what I have seen personally in Brady and the many others I have connected with on Kalydeco, show a highly effective, life-changing drug for eligible mutation types. I have heard individuals bring up the fact that those on Kalydeco still showed some decrease in lung function over time. That is very likely true, but the rate of that decline has been cut in HALF. The long-term data presented at the <a href="http://cysticfibrosisnewstoday.com/2014/06/16/four-studies-vertexs-kalydeco-presented-european-cystic-fibrosis-society-conference/">European Cystic Fibrosis Society Conference</a> still paints a pretty rosy picture, as far as I am concerned. Patients with COPD, asthma, or any other lung disease may experience a decrease in lung function over time also. We may not have achieved perfection with Kalydeco...but we have major improvement. Patients taking Kalydeco first saw a huge jump in lung function, followed by a reduction in the rate of decline. Win. Win.<br />
<br />
<span style="font-size: large;"><b>Closing Thoughts</b></span><br />
<b>*</b>I believe that The CF Foundation is fighting exorbitant drug pricing in the best possible manner within our system--by investing in competition. If we want to be in the game at all, we have to follow the free market rules, and you've got to play to win! I will also argue that CFF execs are worth every penny they are paid.<br />
<br />
<b>*</b>Kalydeco wouldn't exist without the venture philanthropy model--which has fueled a large part of the CFF's drug development success.<br />
<br />
<b>*</b>Vertex is behaving as many businesses do (despicable, but not overly surprising). They have a blockbuster in their hands now with Kalydeco, and a recent failure with Incivek. As far as anyone knows, they haven't done anything illegal. <br />
<br />
<b>*</b>Lastly, I could never describe how deeply I appreciate the work done at Vertex Pharmaceuticals. I mean, I have their molecule tattooed on my left foot. All I am saying...is that it is my one and only tattoo, and I have plenty of empty real estate where I can place the next amazing compound that comes around! I would love nothing more than to see my precious <i>Kalydeco</i> become obsolete (and cheap) when a competitor drug maker eventually comes to market with an even more effective potentiator! Please be respectful in your comments, and remember that I represent no one but myself.<br />
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<span style="font-size: large;"><b>For Reference</b></span><br />
<br />
Here are some of the publications referenced within the blog...if you are looking for some more light reading. <br />
<br />
This article, "<i><a href="http://jeromegroopman.com/ny-articles/OpenChannels-CF-050409.pdf">Open Channels</a></i>," was in The NewYorker Magazine in 2009, and details the CFF's financial involvement in the development of Kalydeco, and demonstrates the unique leadership style of the CFF execs. <br />
<br />
"<i><a href="http://www.medpagetoday.com/Pulmonology/CysticFibrosis/39217">Cystic Fibrosis: Charity and Industry Partner for Profit</a></i>." This article explains the "venture philanthropy model" and outlines potential conflicts of interest.<br />
<br />
"<i><a href="http://www.forbes.com/sites/edsilverman/2012/06/11/the-curious-timing-of-those-vertex-stock-sales/">The Curious Timing of those Vertex Stock Sales</a></i>," describes the questionable stock sales that led to the SEC probe.<br />
<br />
"<a href="http://www.jsonline.com/watchdog/watchdogreports/charitys-investment-a-prescription-for-profits-for-drug-maker-p79tfc9-208027961.html">Charity's Investment a Prescription for Profits for Drug Maker</a>." More info on Vertex stock profits, orphan disease drug development, and financial entanglement with industry. <br />
<br />
<a href="http://www.washingtonpost.com/national/health-science/drugmakers-find-breakthroughs-in-medicine-tailored-to-individuals-genetic-makeups/2014/06/01/40127d1c-e107-11e3-8dcc-d6b7fede081a_story.html">Drugmakers Find Breakthroughs in Medicine Tailored to Individuals' Genetic Makeups</a> was published in The Washington Post on June 1st, and discusses the expensive new era of genetic medicine. <b><i>Brady's Kalydeco Story</i></b> is featured in this article! <br />
<br />
"<a href="http://www.forbes.com/sites/johnlamattina/2013/11/04/vertex-failure-shows-biotech-is-not-immune-to-big-pharma-type-layoffs/">Vertex Failure Shows Biotech is Not Immune to Pharma Type Layoffs</a>" Describes some of the damage control measures taken by Vertex to stay in the game. <br />
<br />
"<a href="http://www.theglobeandmail.com/life/health-and-fitness/health/kalydeco-a-miracle-drug-with-a-catch/article19278862/">Kalydeco: A Miracle Drug With a Catch</a>" describes access struggles in Canada.<br />
<br />
In "<a href="http://www.aww.com.au/diet-health/health-news/2013/12/the-miracle-drug-that-has-changed-my-life/">The Miracle Drug That Has Changed My Life</a>," read about access issues in Australia, and the absolute cruelness of the delays caused by continued price negotiations.<br />
<br />
"<a href="http://www.charitywatch.org/hottopics/Top25.html">Top 25 Compensation Packages</a>" from The American Institute of Philanthropy reports on salaries of non-profit leaders. <br />
<br />
"<a href="http://www.pbs.org/wgbh/nova/body/cracking-your-genetic-code.html">Cracking Your Genetic Code</a>" is an awesome PBS NOVA special, that features Kalydeco story about mid-way through. AN ABSOLUTE MUST SEE!<br />
<br />
"<a href="http://cysticfibrosisnewstoday.com/2014/06/16/four-studies-vertexs-kalydeco-presented-european-cystic-fibrosis-society-conference">Four Studies of Vertex's Kalydeco</a>" presented at The European Cystic Fibrosis Society Conference this June. Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com5tag:blogger.com,1999:blog-7535774120903384819.post-86775041335731823892014-06-24T16:33:00.000-07:002014-06-24T17:04:53.845-07:00Pure SpeculationVertex released the data from their pivotal phase 3 combination trial today (VX-809 + VX-770), and reported "positive outcomes." There has already been a huge amount of discussion about it on social media, so here is my opinion...<br />
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First of all, let's be clear about these <a href="http://investors.vrtx.com/releasedetail.cfm?ReleaseID=856185">results</a>--they are modest improvements. This combination does not offer the same MAGNITUDE of results that Kalydeco did for G551D patients (but neither researchers nor the CFF expected it to). Vertex knew prior to the trial, what the FDA would consider "statistically significant" improvements. With the combo's relatively lackluster results in phase 2, everyone seemed to predict that the numbers from phase 3 would be "a close call," or just BARELY reach that significant threshold. As hard as I have tried to pry for inside info on this trial, I was never able to get anyone "in the know" to give the combo better than a 50% chance of reaching the necessary trial endpoints. I have been on the edge of my seat to see the data--not because I thought it would mirror data from the Kalydeco trial, but because I simply hoped it would be GOOD ENOUGH for FDA approval (and that is yet to be seen!). It would be wonderful if every drug that came to market from this point forward were as effective as Kalydeco is for G551D, but I don't think that is a realistic expectation. A reduction in pulmonary exacerbations by approximately 1/3 in the combo trial treatment group seems pretty significant to me, and a reason to celebrate this news! My hope is that combo serves to stabilize/improve lung function for many with CF while BETTER drugs work their way to market! Even if this is not the perfect drug, it may be a way to--<br />
1) Buy some precious time for thousands of CFers by stabilizing or improving lung function,<br />
2) Increase media focus on curing CF,<br />
3) Keep fundraising momentum going, and<br />
4) Maintain hope within the CF community about future advancements. </div>
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Once the new drug application is submitted (Vertex says "last quarter of this year"), the FDA ruling should come very quickly thanks to the newly designated "<a href="http://www.fda.gov/regulatoryinformation/legislation/federalfooddrugandcosmeticactfdcact/significantamendmentstothefdcact/fdasia/ucm341027.htm">breakthrough</a>" status this combo holds. Breakthrough is the most expedited review the FDA offers, and only a few drugs have been approved. Recently, Novartis' cancer drug <a href="http://www.fiercebiotech.com/story/novartis-grabs-early-fda-approval-lung-cancer-drug-zykadia/2014-04-29">Zykadia</a> was granted Breakthrough status, and on the market about 6 weeks later! Vertex has a good working relationship with the FDA. In other words, if the FDA approves this drug, a ruling could happen FAST--maybe even by the end of this year!</div>
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If the FDA approves the drug for marketing, it will almost certainly be labeled exclusively for homozygous DF508 patients. I am really curious to see where they set their price point for this drug. In an investor conference call I listened about 2 years ago, Vertex claimed they "set the price of Kalydeco based on the estimated benefit of this drug, for the limited population size." So...does that mean that they are going to lower the price for the combo because the population group is much larger?? I doubt it. Call me a naysayer, but when I see that $30K pricetag attached to Brady's Kalydeco statement each month, and see the access battles that have been waged abroad, I have little faith that they won't try to wring every last penny out of this drug also. I worry how INSURERS are going to react to when 15,000 CF patients want access to drugs in the "ultra-expensive" category. A large % of the CF population is on Medicaid, which comes back to taxpayer dollars. There could be some push back for coverage--especially if it only has modest benefits, or ethical questions raised about who pays for these pricey advancements. We are entering uncharted territory. This is why it is more important than ever to be an <a href="http://nu.salsalabs.com/o/50674/p/salsa/web/common/public/signup?signup_page_KEY=6843">advocate</a> for CF! </div>
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I'm sure that some people are disappointed by the small increase in lung function reported in the Vertex data today. Of course, everyone wishes that number was larger. I maintain that these results are basically what was expected with the increasing knowledge of the DF508 specific CFTR dysfunction, and data from earlier phase trials. Looking forward, I've already seen plenty of evidence that "second generation" combinations (many of which have already been tested in the laboratory), are several years away, but represent the huge clinical benefits we all hope for in this new treatment era. In a nutshell, here is why--</div>
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There are a couple of problem sites within the folded structure of DF508 CFTR. </div>
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VX-809 addresses one of those problems, which enables a small amount of CFTR to pass through "quality control" (endoplasmic reticulum) in the cell and make it to the cell surface--where Kalydeco acts on the protein to "open the gate" and allow Chloride ions to pass through. Even further benefit might be seen if we could stabilize the protein at the surface, and prevent premature unraveling. </div>
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Researchers discovered a ceiling of benefit when correcting only one site, and found that adding a second corrector compound to the mix to treat the other problem area, GREATLY increased the amount of CFTR that was able to reach the cell surface--where Kalydeco did it's job like a champ and opened that gate for a large amount of Chloride to flow through.</div>
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It shows that a 3 drug combo restored about 58% CFTR function in the lab.</td></tr>
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These "second generation" combos are the ones that are going to give a lot of double deltas the magnitude of results they are hoping for...but for now, I'm going to celebrate a LITTLE BIT of improvement for SOME people with CF! This is progress!</div>
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In the near future, we will also hear more about the VX-661/VX-770 combination. In some ways, VX-661 is known to be a superior corrector compound to VX-809. VX-809 is not highly compatible with VX-770 (The presence of VX-809 degrades the action of VX-770. To get an effective dosage of VX-770, they had to pump up the initial dosage to 250 mg.--100 mg. more than the standard dosage for Kalydeco monotherapy. Anytime you increase drug dosages, you run the risk of increased problems with metabolism by liver and kidneys, or other side effects). VX-661 does not have this type of interaction with VX-770, and just seems to work better in general. This two drug combo would still be considered "first generation," but could at least represent an option for some folks sooner than a second generation combo. <br />
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<tr><td class="tr-caption" style="text-align: center;">From this year's Volunteer Leadership Conference<br />
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<span style="font-size: small;">The bar was set extremely high when our first venture into gene modification resulted in Kalydeco. The announcement today may not live up to those expectations, but I would be thrilled to see the FDA approve this combo and give 50% of the CF population an opportunity to at least TRY a genetic modifying compound to see whether (or not), it works for them. I AM CELEBRATING a step forward today! Cheers to The CFF! Vertex Pharmaceuticals! And all the individuals and families that donated time and/or money to make this possible! </span></div>
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Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com10tag:blogger.com,1999:blog-7535774120903384819.post-24936475243207412862014-03-01T14:10:00.001-08:002014-03-01T14:22:11.750-08:00A Different FilterMore than 2 years have gone by since Brady began taking Kalydeco. I want to take the opportunity to recap what life looked like for Brady pre-Kalydeco, back in February, 2012...and compare it Brady's reality now. <br />
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<span style="font-size: large;"><b>Brady's Status--Pre-Kalydeco, Age 4 1/2 </b></span><br />
Kalydeco was approved by the FDA on January 31st, 2012. Brady took his first dose on February 10th, 2012.<br />
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<b>Lung Health:</b> Brady had very good lung health. He had always presented with "clean/normal" cultures, and did not have any baseline cough. A chest CT scan performed 1 month after beginning Kalydeco showed "no visible structural damage" to his lungs. The hope was that initiating a treatment like Kalydeco at this earliest stage of lung disease may actually be able to PREVENT disease progression. Prior to beginning Kalydeco, Brady's nebulizer schedule was:<br />
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<i><b>Morning</b>-Albuterol, Pulmozyme, and Hypersal (7%), followed by 20 min. in the Vest machine, for a total treatment time of 45-60 min.</i><br />
<i><b>Evening</b>- Albuterol and Hypersal (7%), followed by 20 min. in the Vest. Total time 30-45 min.</i><br />
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<b>Upper Respiratory Health</b>: Brady may have enjoyed good lung health at that time, but had a really tough time with upper respiratory inflammation. Brady had undergone 2 surgeries as a 4 year old--tonsil/adenoidectomy, and an endoscopic sinus clean-out. He had aggressively growing polyps that had completely shut off the air flow through his sinuses. The polyps grew so large that they had begun thinning and shifting his delicate facial bones. A CT scan of his sinuses showed that there was a risk of the polyps actually breaking through the eye socket on one side, and causing potential eye or brain damage. Not cool. The sinus polyps had also completely robbed Brady of his sense of smell. He snored, snorted, and struggled to breathe at night and woke up frequently. Brock and I could hear every breath he took at night, and we also struggled to sleep. Brady never complained about any pain associated with the polyps, but I can't imagine that this felt good.<br />
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<i><b>He took frequent bursts of Prednisone and antibiotics to deal with upper respiratory inflammation/infection and we used a device called "The Nasatouch" to irrigate his sinuses with steroids 3 times a day. </b></i><br />
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I think the Nasatouch is an extremely useful device, but irrigating a 4 year old's sinuses, 3 times a day, is honestly just one step away from full blown HELL. We basically had to hold Brady down like a criminal and shoot steroids into each nostril--10 seconds on each side. I'm sure it burned and wasn't very much fun...but we did it. Even with all our efforts to keep his sinuses open, the polyps began growing back just a few months after the surgery to remove them. When Kalydeco was approved, Brady had just finished a Prednisone burst for inflammation, but it wasn't helping enough. His sinuses were definitely getting bad again. We had an appointment with his ENT coming up, and we were all dreading the thought of going through another sinus surgery.<br />
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<b>Digestive Health</b>: Like many people with CF, Brady had severe pancreatic insufficiency. I can pinpoint the exact day that his pancreas became completely clogged with mucus, and he stopped being able to digest food on his own (when he was between 2-3 weeks old). He stopped gaining weight and began having all sorts of digestive distress. He had already tested positive on the newborn screen for CF by this time, and was diagnosed with CF and put on digestive enzyme replacements within a week. Brady was not born with meconium ileus, but he did have several soft/partial bowel blockages in the first 4 years of his life. Like many with CF, I think he suffered with some low grade stomach pain and irregularity, as a rule. Still, Brady was doing pretty well nutritionally, and his Dr. was pleased with his weight and height at age 4.<br />
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<i><b>Brady's gut functioned best when he was taking approximately 2000 units of lipase/Kg body weight, at meal times</b></i>.<br />
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Then it happened. Our family was on vacation in Arizona when Kalydeco was approved by the FDA, ahead of schedule. We were in a small town called Verrado, just west of Pheonix when we heard the news. Within a week, we had gotten a prescription and insurance approval. We rushed home for a baseline visit with Brady's Dr., so he could begin the drug immediately. <br />
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<span style="font-size: large;"><b>Brady's Status Today, 2+ years taking Kalydeco. Age 6 1/2</b></span></div>
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<b>Lung Health</b>: In the past two years, we have slowly eliminated almost all nebulizer treatments. Currently, Brady does 2 puffs of Albuterol with a Vortex spacer, and a single vial of Pulmozyme, once a week, for maintenance. The environment in his lungs has changed so drastically, that he can no longer tolerate 7% Hypersal, and we don't use it at all anymore. We also questioned whether or not Brady needed Pulmozyme for maintenance, and decided to slowly taper down from this medicine also. I feel really comfortable doing it once a week, and having it on hand in case Brady comes down with a virus (if he gets gunky, we will do Pulmozyme daily until the virus is gone). His current schedule looks like this--</div>
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<i><b>Morning</b>-15 minute session on the Vest is all we do on most days. Once a week he does a vial of Pulmozyme before the Vest.</i></div>
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<i><b>Evening</b>-We do NOTHING to manage CF. </i></div>
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It has been really difficult for all of us (my husband, myself, and Brady's CF Dr.) to make some of these decisions about how to proceed with Brady's treatment schedule. We have every indication that Kalydeco is working great for Brady, but the LAST thing we want to do is remove a medicine that he still needs. Because Brady started Kalydeco in a place of excellent lung health--no known bacterial colonizations, no baseline cough, and a CT showing no structural damage--we hoped that Kalydeco alone might be enough to maintain his lung health and free him from the progression of CF lung disease. Last week, we did another chest CT scan to offer us some feedback. </div>
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<span style="font-size: large;"><i>I am ecstatic to report that the chest CT scan from last week was identical to his scan 2 years ago--<b>NO VISIBLE STRUCTURAL LUNG DAMAGE</b>. </i> </span></div>
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There is plenty of documented evidence that CF lung disease can progress in the absence of symptoms, so we were really relieved that his lungs seem to be doing so well without daily maintenance (beyond that little blue pill!). We feel a little more confident that we are following the appropriate path to maintain his lung health...and have the highest hopes that this will continue as long as he maintains functional CFTR with Kalydeco. </div>
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<b>Upper Respiratory Health</b>: The upper respiratory inflammation that Brady had battled for years came to a screeching halt just a few days after beginning Kalydeco. He was breathing freely through his nose within a week of starting K, and he hasn't needed steroids or antibiotics for his sinuses at all since then. He stopped snoring at night and regained his sense of smell. He never needed the next sinus surgery we saw looming on the horizon. We stopped using the Nasatouch device and currently do absolutely NOTHING to manage this former "headache". He is completely free of sinus polyps, and sinus symptoms. It has been remarkable. </div>
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<b>Digestive Health</b>: When Brady first began taking Kalydeco, we noticed some constipation (similar to what might be seen with an increase in enzyme dosage). We wondered if Kalydeco had affected his ability to secrete digestive enzymes into the small intestine. There is the <i>hope</i> that in patients without too much pancreatic scar tissue, some function might be restored with a drug like K, that works to thin secretions. We experimented with lowering his enzyme dosage a bit, but ultimately decided that his gut still functions best with a similar enzyme dosage as always--approx 2000 lipase units/Kg body weight with meals. To confirm this, we repeated a fecal elastase test last week, and weren't surprised to learn that Brady still has "severe pancreatic insufficiency." Some patients have been able to reduce enzyme usage with Kalydeco. I have even heard of some patients being able to stop altogether with enzymes...but not Brady. His pancreatic damage seems "irreversible" at this point. With that said, I can't stress how much IMPROVEMENT we have seen with his digestive function! He hasn't seen a huge weight increase like some patients experience, but it is important to note that he started out with excellent growth percentiles. So if Kalydeco hasn't improved his pancreatic function...why have we seen such dramatic improvement in his digestive function? My theory is this--</div>
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1) When CFTR function is restored--the mucus in the digestive tract is restored to a thinner, more watery consistancy (similar to the normalization of lung mucus). You can imagine that excessive, thick sticky mucus in the gut does NOT promote digestion and absorption of nutrients (in the same way that excessive thick mucus in the lungs does NOT promote the transfer of oxygen). Less mucus = better absorption.</div>
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2) CF patients typically have an overly acidic environment in both the lungs and gut, resulting in a cascade of chemical imbalances. In the lung, an overly acidic environment reduces the lung's own natural "killing power" of foreign microbials. In the intestines, the overly acidic environment causes problems with the efficacy of enzyme replacements. The enzymes beads are designed to remain intact in an <i>acidic</i> environment (so that they can survive the stomach acid), and dissolve only when the environment turns basic. In healthy individuals, bicarbonate is released as food passes from the stomach into the small intestine, changing the environment from an acidic pH to a basic pH. This is where digestive enzymes beads SHOULD dissolve (or where a healthy pancreas secretes natural digestive enzymes) to break down food. Individuals with CF often have a difficult time achieving the "basic" environment needed to dissolve the enzymes and allow them to work as well as they can. Many patients take acid blockers like Prevacid or Prilosec to help lower their overall acidity and help their enzyme replacements work better. Researchers have shown that patients taking Kalydeco were able to restore an optimal pH to their intestine, thereby maximizing the benefit of their enzyme replacement therapy. In other words, Brady is still taking the exact same dosage of enzymes, but they are actually WORKING far better. This normalized pH, in combination with the thinning of intestinal mucus has improved his digestive function greatly. Brady's growth has continued at a healthy pace, and everything in the bathroom has been very "normal" (huge contrast from some of the unusual things I saw come out of that child before!) since Kalydeco came into our lives. </div>
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As far as we are concerned, the changes in Brady's health over the past 2 years have been truly amazing. I am so encouraged by his latest CT scan, and overall well being. For my husband and I, finding our <i>new normal</i> has been surreal process. This winter, we went back to the same small town in Arizona, where we were vacationing when Kalydeco was approved in 2012. In my mind, Verrado, Arizona is a magical place. We were so excited to go back, and in many ways, life looked very much the same...</div>
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<tr><td class="tr-caption" style="text-align: center;">We looked at dino bones before Kalydeco...</td></tr>
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<tr><td class="tr-caption" style="text-align: center;">Then we did it again 2 years later.</td></tr>
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<tr><td class="tr-caption" style="text-align: center;">We took desert hikes in 2012 before Kalydeco...</td><td class="tr-caption" style="text-align: center;"><br /></td><td class="tr-caption" style="text-align: center;"><br /></td><td class="tr-caption" style="text-align: center;"><br /></td><td class="tr-caption" style="text-align: center;"><br /></td><td class="tr-caption" style="text-align: center;"><br /></td><td class="tr-caption" style="text-align: center;"><br /></td><td class="tr-caption" style="text-align: center;"><br /></td><td class="tr-caption" style="text-align: center;"><br /></td><td class="tr-caption" style="text-align: center;"><br /></td><td class="tr-caption" style="text-align: center;"><br /></td><td class="tr-caption" style="text-align: center;"><br /></td><td class="tr-caption" style="text-align: center;"><br /></td><td class="tr-caption" style="text-align: center;"><br /></td><td class="tr-caption" style="text-align: center;"><br /></td></tr>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhwRbniRFXJ1HQU1cGaaa61N-vRDe2sKW97btrE0K-ODEgR6rUEzF4wdWrPBKxDiZd0W33Q6ncaMPU0qNYGJzp6Uc0TD9Xggl5XW8SYuqM_0G5PU606V4hy9nK7bO_8oqxefY0cpRj8ntc/s1600/brock's+phone+447.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhwRbniRFXJ1HQU1cGaaa61N-vRDe2sKW97btrE0K-ODEgR6rUEzF4wdWrPBKxDiZd0W33Q6ncaMPU0qNYGJzp6Uc0TD9Xggl5XW8SYuqM_0G5PU606V4hy9nK7bO_8oqxefY0cpRj8ntc/s1600/brock's+phone+447.jpg" height="300" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">And did the same hikes in 2014.</td></tr>
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<tr><td style="text-align: center;"><img alt="" class="spotlight" height="225" src="https://scontent-a-sea.xx.fbcdn.net/hphotos-ash2/t1/395232_10150565828862402_1743162996_n.jpg" style="margin-left: auto; margin-right: auto;" width="400" /></td></tr>
<tr><td class="tr-caption" style="text-align: center;">He fed Giraffes before...(age 4 1/2)</td></tr>
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<tr><td style="text-align: center;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj_cKYRxfGTJZFHNinj8MDMo-xLHeUVQAO8mB97Z-9qkE0MQpr46nh-mywRzHp6wnhWWW_s_3ohgVwMJjYdeGbAk0RPXWRj7KfoOjuOzfPJQ_AnkCYv96yfl72-kEpuEtU1OYFKkmcZf90/s1600/20140128_153624.jpg" height="300" style="margin-left: auto; margin-right: auto;" width="400" /></td></tr>
<tr><td class="tr-caption" style="text-align: center;">And then did it again. (age 6 1/2)</td></tr>
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Brady has grown so much, and he doesn't have his "Prednisone face" anymore, but otherwise you would never guess how much has truly changed in our lives over the last 2 years--all the invisible <i>time, energy, sleep</i>, and<i> peace of mind</i> Kalydeco has given to us. Look more closely and you will see that the pictures are actually very different--to me, it feels as if Kalydeco has given us a <i>new filter</i> for the camera lens. This filter is much less burdensome to carry, and every photo is enhanced by the warm glow of <i>relief and gratitude</i>. </div>
Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com7tag:blogger.com,1999:blog-7535774120903384819.post-85237552853674523332013-10-26T18:25:00.001-07:002013-10-26T18:25:21.766-07:00Up for Debate<div class="separator" style="clear: both; text-align: center;">
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Every year at the NACFC, one symposium session is dedicated to debating hot topics in CF clinical care. This year's symposium addressed three important issues, where specialists have significant differences in opinion. One expert presents the PRO argument, another presents the CON argument, and then the audience "votes" for the winner by applause.<br />
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<b>This year, 3 important issues were debated</b>--<br />
1) Can Exercise Substitute for Airway Clearance?<br />
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2) Which should be the first drug introduced to manage CF--Hypertonic Saline or Dornase Alfa (Pulmozyme)?<br />
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3) Should glucose intolerance be treated aggressively in CF, or not? <br />
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I love these debate sessions each year because they expose the wide range of opinions that exist among CF professionals regarding the "right" way to treat patients. Some people never question their Doc, because it is assumed that they always know best... These sessions help illustrate why CF care can vary so much from center to center! Feel free to put in your two cents on any of these topics in a comment!<br />
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<i><span style="font-size: large;"><b>Can Exercise Substitute for Airway Clearance?</b> </span></i><br />
<u><b>Pro argument</b></u> given by Dr.Cecilia Rodriguez Hortal.<br />
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For the purposes of this argument, Dr. Hortal suggests that vigorous exercise, <b>with built in breaks for patients to "huff cough" and expectorate mucus</b>, could be used as an alternative to regular airway clearance techniques, particularly in pediatric populations with milder lung disease. She discusses the success of the "Swedish model"--which utilizes exercise and specialized breathing techniques as a form of airway clearance. She also presents a few scientific studies showing the benefits of physical exercise on CF lung disease. Exercise has been proven to reduce the viscosity of mucus, improve airway hydration, increase cilia beat frequency in the airways, and reduce markers of inflammation.<br />
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Dr. Hortal goes on to explain that physical exercise (both aerobic and anaerobic) offers health benefits far beyond airway clearance, and can be a fun, non-stressful way for patients to perform their airway clearance. In her opinion, exercise is a more kid-friendly technique that could encourage patients to develop healthy habits for life. She goes on to discuss one scientific study which showed exercise to be as effective as regular airway clearance techniques for children with CF. </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgR1HTOTuiIWvoDhItBzyHZoAiyE9-sy8ETsogtRCyKS4mBC9Oli1vcdKGuT_-FqeJAFxa8eWsJ7jy-0wk9gHrjGzDMgf5vxiNLFoLpneMSX0-o7xDdX-2a-sb2ezpy354bXSGpz7evn34/s1600/20131018_104001.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="300" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgR1HTOTuiIWvoDhItBzyHZoAiyE9-sy8ETsogtRCyKS4mBC9Oli1vcdKGuT_-FqeJAFxa8eWsJ7jy-0wk9gHrjGzDMgf5vxiNLFoLpneMSX0-o7xDdX-2a-sb2ezpy354bXSGpz7evn34/s400/20131018_104001.jpg" width="400" /></a></div>
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<span style="font-size: large;"><i><b>Can Exercise Substitute for Airway Clearance?</b> </i> </span></div>
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<u><b>Con argument</b></u> presented by Dr. Shruti Paranjape</div>
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First, Dr. Paranjape presented the current guidelines for Airway Clearance Therapy:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhy0jimfwa3YQkkjvEfbKBLz3WgxnYDtnS3ljlFpWK4AAdVcmADFQi4tSKU_yrve9eq5aXDpRubq2BgjrwSgIJDvCbVGsB7AVwqHh4AmHpYcK2_ZTY9wOfSUIcT24rQu5YfTVrZXfdX3NM/s1600/20131018_104323.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="300" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhy0jimfwa3YQkkjvEfbKBLz3WgxnYDtnS3ljlFpWK4AAdVcmADFQi4tSKU_yrve9eq5aXDpRubq2BgjrwSgIJDvCbVGsB7AVwqHh4AmHpYcK2_ZTY9wOfSUIcT24rQu5YfTVrZXfdX3NM/s400/20131018_104323.jpg" width="400" /></a></div>
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He went on to explain that there are many methods currently available for effective airway clearance, and that the selection of technique should be tailored to meet the individual patient's needs. </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiFcbxYcdbKPS0cLBWbHxZZsTHmXBqMEXpNcfvJyVTafWYQtvufa3-OuAleETt11RQwdqYWNTxg-DXKDu07hpxUuua70sy3IOpcncudI7x5044vzoFd4NduIaKAye6lnV0sXPKZic5Q_hg/s1600/20131018_104413.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="300" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiFcbxYcdbKPS0cLBWbHxZZsTHmXBqMEXpNcfvJyVTafWYQtvufa3-OuAleETt11RQwdqYWNTxg-DXKDu07hpxUuua70sy3IOpcncudI7x5044vzoFd4NduIaKAye6lnV0sXPKZic5Q_hg/s400/20131018_104413.jpg" width="400" /></a></div>
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Even though Dr. Paranjape was presenting the CON argument in this debate, he spent a lot of time discussing the irrefutable benefits of exercise in the CF population. Dr. Paranjape believes that exercise should absolutely be promoted to improve the health of CF patients--but should be an adjunctive therapy rather than a replacement for airway clearance. </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiejI_xCV35yUQ97XBxZW2-Qz9dqkMEXtteuJqWLlHzq-ybvUNZsflrwvAAdZMMiAIj_sMsSmP7MlFMnsST8UCOghXt1NPKus1-Am7frdOsjacmPGhpsdpJPZECS9aREjCsVX7Rn4WZl-Q/s1600/20131018_104513.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="300" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiejI_xCV35yUQ97XBxZW2-Qz9dqkMEXtteuJqWLlHzq-ybvUNZsflrwvAAdZMMiAIj_sMsSmP7MlFMnsST8UCOghXt1NPKus1-Am7frdOsjacmPGhpsdpJPZECS9aREjCsVX7Rn4WZl-Q/s400/20131018_104513.jpg" width="400" /></a></div>
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In the end, both presenters agreed that exercise is an extremely beneficial part of the CF care regimen, but Dr. Paranjape believes exercise should be thought of as an additional "prescription," rather than a replacement for other airway clearance therapies. There was some discussion about the technique required to move mucus from the peripheral lung (small airways) to the central lung, where it could be coughed out. Apparently, this peripheral lung clearance happens best during periods of long <i>expiration</i> (long breaths out). There was concern that if a patient was exercising at an aerobic level, respiration rate would be too rapid for peripheral lung clearance to effectively occur. It seemed that Dr. Paranjape won the audience vote by applause. </div>
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<b><i><span style="font-size: large;">Which drug should be the first used to treat CF?</span></i></b></div>
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<u><b>Hypertonic Saline argument </b></u>given by Dr. Margaret Rosenfeld.</div>
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Dr. Rosenfeld began her argument by showing some data from the ARESTCF study conducted in Australia. This revealing study showed that structural lung damage and decreased lung function occur very early in children with CF--even in the absence of symptoms. Furthermore, this lung damage was found to be progressive. The ARESTCF study scared me big time when I first saw the data presented at the 2011 NACFC and I wrote a whole blog entry about it: </div>
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<a href="http://luckycfmom.blogspot.com/2012/03/cf-lung-disease-does-symptomless-safe.html">http://luckycfmom.blogspot.com/2012/03/cf-lung-disease-does-symptomless-safe.html</a> The ARESTCF study utilized CT scan to detect structural lung damage like bronchiectasis in infants with CF. They also utilized the <u>B</u>roncho<u>A</u>lveolar <u>L</u>avage (BAL) technique to determine the microbiome in the CF infant lung. BAL is much more sensitive and accurate at detecting infection than the more commonly used oropharyngeal "throat swab." BAL found that infants with CF begin colonizing harmful bacteria long before symptoms appeared, and prior to testing positive for infection on a throat culture. </div>
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The idea is that earlier intervention may be able to PREVENT bronchiectasis (irreversible widening of the airways). Dr. Rosenfeld believes that Hypertonic Saline is an attractive candidate for first use because it has been shown to hydrate mucus--improving mucociliary clearance. </div>
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She shows that Hypertonic Saline acts fairly early in the cascade of dysfunction that leads to disease in the lungs, by improving water absorption. </div>
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She also shows evidence that Hypertonic Saline has a positive impact on reducing exacerbations in patients over the age of 6...</div>
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...But Dr. Rosenfeld has one big strike against her in this argument, and she acknowledges the results of the ISIS study--which failed to show any benefits of Hypertonic Saline use in infants. </div>
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Dr. Rosenfeld believes that the endpoints of the ISIS study may not be the most appropriate to show true benefit in this age group, and suggests that further studies, using alternate endpoints like LCI (Lung Clearance Index, which has been shown to be a much better prediction of lung function in infants than FEV or exacerbation status) or CT scan, may support use of this cheap, readily available drug in the infant population. After her call for further studies, Dr. Rosenfeld sort of concedes her position before the other presenter even takes the mic!</div>
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<span style="font-size: large;"><i><b>Which drug should be the first used to treat CF?</b></i></span></div>
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<u><b>Dornase alfa argument </b></u>presented by Dr. Ran Anbar</div>
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Dr. Anbar opens with a little refresher course on what Pulmozyme is designed to accomplish in the lungs. Neutrophils are white blood cells, which attack foreign organisms in the human body. Neutrophils are an essential part of fighting infection, but these cells also secrete harmful substances that can cause lung damage (neutrophil elastase). Neutrophil levels can be elevated in CF lungs, and when these cells die, they leave behind long strands of DNA that act to bind together thick sticky mucus (think about adding a bunch of cooked spaghetti to your jello mold--it is going to strengthen that otherwise flimsy structure. All those internal connections encourage formation of the mucus "biofilm."). Pulmozyme is designed to cut up the long strands of extracellular DNA left behind by neutrophils, allowing for better mobilization of mucus. Dr. Anbar then goes on to present the evidence of Pulmozyme's benefits in patients. For example, studies show that Pulmozyme slows the rate of lung function decline in CF, and also reduces the burden of infection.</div>
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<tr><td class="tr-caption" style="text-align: center;">Dr. Anbar says that Pulmozyme interrupts the vicious cycle of infection, inflammation, and obstruction in two crucial ways.<br />
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In conclusion, Dr. Anbar felt that the evidence for Dornase alfa to be the first drug used to treat CF was on his side, and the audience agreed. I am, however, still curious to see what benefits might be seen using Hypertonic Saline in infants if different study endpoints were selected. For now, Pulmozyme got the win from this crowd. </div>
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The last question debated dealt with the topic of treating glucose intolerance in CF patients.</div>
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<b><i><span style="font-size: large;">Non-fasting Hyperglycemia Should be Treated Aggressively.</span></i></b></div>
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<b><u>Pro argument</u></b> given by Dr. Deepa Kirk.</div>
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Dr. Kirk, an adult endocrinologist, explained that there are guidelines to treat full blown Cystic Fibrosis Related Diabetes (CFRD)--but there is a grey area when it comes to treating early signs of glucose intolerance in CF. She explains that CFRD develops differently than Type II diabetes. Rather than a linear progression to disease, glucose tolerance in CF patients sort of toggles back and forth between normal range and CFRD range. </div>
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She explains that glucose intolerance is also known as "pre-diabetes," and in other patient groups (pregnant women, steroid treated patients, the elderly) there is evidence that early treatment can have a positive effect on patient health. Dr. Kirk goes on to explain how untreated hyperglycemia (high blood sugar), can lead to impaired lung function and further impairment of insulin regulation. </div>
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Dr. Kirk described some small studies on CF patients that showed patients with impaired glucose tolerance gained weight and improved pulmonary function after initiation of insulin therapy. Since BMI and pulmonary function often begin to decline YEARS before a diagnosis of CFRD, Dr. Kirk feels that early interventions to improve sugar control could lead to an overall improvement in health outcomes for patients. She notes that untreated hyperglycemia can cause unpleasant quality of life issues for patients that should also be considered (headaches and fatigue). She maintains that early interventions would not necessarily have to be as burdensome as managing constant insulin injections--in fact, the first therapies for impaired glucose tolerance may likely be dietary modifications, oral meds, or low dose insulin. </div>
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<span style="font-size: large;"><b><i>Non-fasting Hyperglycemia Should be Treated Aggressively</i></b></span></div>
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<u><b>Con argument</b></u> given by Dr. Irl Hirsch</div>
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Dr. Hirsch defends the current line of thinking in the CF world right now, which is that non-fasting hyperglycemia does NOT warrant aggressive treatment. First, he describes the criteria used to officially diagnose diabetes--hyperglycemia resulting in vascular damage known as retinopathy. He argues that CF patients with non-fasting hyperglycemia do not present with retinopathy. He goes on to explain the huge range of glucose levels considered normal or "average." He claims that it is completely unclear how much of the "complications pie" in CF comes from impaired glucose tolerance, and that there is no data to support insulin therapy in this group. Dr. Hirsch claims that the link between impaired glucose intolerance and lung function represents a "chicken or egg" argument. Will interventions to improve sugar control improve lung function? Or do unstable sugars simply go along with worsening CF lung disease and steroid use? Dr. Hirsch feels that the treatment burden associated with an insulin intervention is too high for the modest benefits that might be seen by patients. The crowd vote was pretty evenly split between the two presenters. Regardless of the outcome of this debate, I think CFRD and glucose intolerance are going to be topics that we will hear more and more about in the coming years as scientists unravel the mechanism behind CFRD. </div>
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No wonder it is so difficult to determine the "correct" way to treat CF...even the experts disagree! I hope this entry inspires some further debate on these topics--ideally with your own clinical team! What additional perspectives could patients add to these pro/con arguments? </div>
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<br />Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com2tag:blogger.com,1999:blog-7535774120903384819.post-88863183377715932232013-10-25T20:56:00.000-07:002013-10-25T20:56:05.926-07:00The Breastfeeding EffectThe Conference may be over, but I am going to keep the information coming! I am trying to overcome the feeling that I need to sit down and write this huge novel for a proper blog post...so this entry will focus on information from a single discussion I watched at the NACFC entitled: The Developing Gut and Respiratory Tract Microbiome in Infants with CF. <div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhgutac3DA37byEinGWCf_jW78xxBEY5kV-r_pkM1ldGdOcfdNCMJMofu9tuIHoBPN6497xk-EnJ9Yl7RaL3dGP3XkQXJB4wBRS3UlZga0L5oXijPw4cmVHaJrGjy94hoj06LTXZpLaVVE/s1600/20131018_152658.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="300" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhgutac3DA37byEinGWCf_jW78xxBEY5kV-r_pkM1ldGdOcfdNCMJMofu9tuIHoBPN6497xk-EnJ9Yl7RaL3dGP3XkQXJB4wBRS3UlZga0L5oXijPw4cmVHaJrGjy94hoj06LTXZpLaVVE/s400/20131018_152658.jpg" width="400" /></a></div>
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The term "microbiome" refers to the community of microorganisms that live in our guts and lungs. Healthy biomes are generally non-pathogenic (not disease causing)--they exist in harmony with our bodies. Problems begin to occur in both the gut and lung when certain organisms grow out of control and upset the delicate balance. The biggest variation in the human microbiome occurs during the first 3 years of life. </div>
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Researchers wanted to know:</div>
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1) Do exposure and interventions play a role in the developing microbiome in CF?</div>
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2) Are there patterns within the developing microbiome that predict clinical disease? Do the gut and respiratory microbiomes interact?</div>
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3) Are there targets for a healthier pattern that could help PREVENT early disease?</div>
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The study utilized a relatively small group of patients, and relied on stool and respiratory samples to provide insight into the developing microbiome. An overgrowth of pathogenic organisms in the microbiome is indicative of a CF "exacerbation." </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiZHy1y0kndsbNloNN6UFI3ONSj7ffceEanqkxSr_tdbnJ2fZ7fAu_arzfF9Syvki4BfZBl53SfDD46fGDVK62dkLkRcneyJS167Njc6zx4fkRQtc8eUVeznUx6n_hqRGerSkHcUUv9mUs/s1600/20131018_152944.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="300" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiZHy1y0kndsbNloNN6UFI3ONSj7ffceEanqkxSr_tdbnJ2fZ7fAu_arzfF9Syvki4BfZBl53SfDD46fGDVK62dkLkRcneyJS167Njc6zx4fkRQtc8eUVeznUx6n_hqRGerSkHcUUv9mUs/s400/20131018_152944.jpg" width="400" /></a></div>
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Researchers found that both the digestive and respiratory microbiome increase in diversity over time. There seems to be a relationship between the organisms in the gut and lungs. As researchers began tracking their observations on these infants, they found one factor that seemed to have a strong effect on the stability of the microbiome in both the gut and the lungs--exposure to breast milk. Infants given breast milk had more stable microbiomes. </div>
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In addition, babies exposed to breast milk were able to delay the onset of their first CF exacerbation.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiKJgDs7QJS_aGCqlKuT0z2CyVRgGKY7f02_WRPuDDJaNXekWfcl_AWLKuurt-AowO7yfVQ3GSPEoYLyFC3iWR676YOGs0C-l2L9u5yg9PLXTNB4uVGOQ8DtXndnW_Yr-h_ZumAqNUJU44/s1600/20131018_153542.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="300" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiKJgDs7QJS_aGCqlKuT0z2CyVRgGKY7f02_WRPuDDJaNXekWfcl_AWLKuurt-AowO7yfVQ3GSPEoYLyFC3iWR676YOGs0C-l2L9u5yg9PLXTNB4uVGOQ8DtXndnW_Yr-h_ZumAqNUJU44/s400/20131018_153542.jpg" width="400" /></a></div>
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The breast feeding effect turned out to be so STRONG, that researchers had to statistically correct for breast fed infants, to gain any meaningful data from this study. The presenter called breast milk the "gold standard probiotic," and explained that gut colonization patterns are predictors of lung colonization patterns. The stabilizing effects of breast milk on the gut microbiome seems to spill over to lung microbiome as well. Antibiotic use, on the other hand, did NOT have a significant effect on the microbiome in the gut. </div>
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I felt strongly about sharing this information, because it represents an opportunity for an all-natural "intervention" for infants with CF. I understand that the decision to breast feed, or not, is an extremely personal one...and this entry is not intended to pass judgement. I simply want to share that for the youngest CFers, there is evidence that a dose of nature's gold standard probiotic has been shown to produce meaningful delays to onset of the first respiratory exacerbation. </div>
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Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com3tag:blogger.com,1999:blog-7535774120903384819.post-58693151208175585382013-10-21T20:27:00.001-07:002013-10-21T20:44:04.247-07:00Plenary 3--CFRDThe third Plenary Session of NACFC 2013 explored the topic of <b><u>C</u></b>ystic <b><u>F</u></b>ibrosis <b><u>R</u></b>elated <b><u>D</u></b>iabetes (CFRD) and was entitled: <b>CFRD: From Bench to Bedside & Back again. </b> Andrea Kelly, M.D., MSCE was the first speaker in this session.<br />
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Patients with CF are living longer than ever before (YES!), but age can bring new health issues--including CFRD. CFRD is very common--50% of CF patients will develop it by age 30. Current guidelines recommend annual oral glucose tolerance tests beginning at age 10. <br />
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Insulin secretion defects are present early in CF patients, and are progressive. We know that CFRD doesn't behave exactly like Type 1 or Type 2 diabetes...so what is the mechanism driving the impaired glucose tolerance here? Understanding precisely why so many CF patients develop CFRD could lead to better, earlier therapeutic interventions. After all, CFRD is associated with a lower survival rate and higher rates of lung transplant in CF patients. Not good. Not to mention that CFRD can have a real negative impact on your life. Successfully managing CFRD can be burdensome and time consuming. Symptoms can include decline in BMI and FEV1. <br />
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Some readers might be thinking, "My child is young and her sugars are normal--this doesn't apply to me." Dr. Kelly would argue that it DOES. She goes on to explain the typical oral glucose tolerance test (OGTT)--a sugary drink (75 g glucose) is administered, and after 2 hours, the patient's blood is drawn to test blood glucose levels. Levels below 140 mg/dL are considered normal. 140-199 classifies as "glucose sensitive." Levels above 200 mg/dL are diagnostic for CFRD. Dr. Kelly believes that that the standard OGTT may actually miss many CF patients exhibiting early signs of glucose intolerance and goes on to show some evidence. She suggests that CF patients have an initial delayed and blunted insulin secretion, similar to type II diabetics, and believes early indications of this could be picked up more accurately with the non-fasting, 50g glucose test, where blood glucose is tested after 1 hour instead of 2. Her argument is that early insulin abnormalities can be seen in the time immediately after ingesting glucose, and this test could be better at identifying and treating those individuals exhibiting the earliest signs of CFRD. If dealing with CF has taught me anything, it is that it is almost always better to nip problems in the bud before they get big and ugly. Controlling blood sugars is no exception. <br />
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She went on to describe how pancreatic enzyme replacement has an effect on insulin secretion. Individuals who take their enzymes properly have improved insulin secretion and blood sugar control! Some of those individuals who screen positive for early glucose intolerance might be able to see some improvement by simply tweaking their enzymes a bit (may need support to be diligent in taking them, others may need a dosage adjustment.) That is nice to know. Others may need alternate interventions. <br />
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<span style="text-align: left;">The mechanism driving CFRD isn't completely understood, but Dr. Kelly describes important cells in the pancreas called beta cells--whose primary function is to store and release insulin. Patients with CF have impaired beta cell function. Preserving the function of these cells is crucial to controlling blood sugar levels.</span></div>
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There is also a question whether CFTR function could impact insulin secretion, and Dr. Kelly described a pilot study sponsored by the CFF to answer that question. This study will examine if Kalydeco (Ivacaftor) has a direct impact on insulin secretion.<br />
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Before concluding her discussion, Dr. Kelly mentioned that standard nutritional recommendations for CFers may HASTEN the progression of impaired glucose control and development of CFRD. Patients should still strive to meet the fat/calorie recommendations for CFers, but modifications to carb intake and regular exercise could lead to better glucose control. </div>
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The next speaker in the Plenary session was Dr. John Engelhardt, who works with CF ferrets and CF pigs to gain understanding to the mechanism behind CFRD. CF pigs and ferrets develop lung and pancreatic disease similar to humans, and provide an effective model of study. Newborn pigs have severe pancreatic disease. Ferrets have milder disease, but rapidly develop disease and pancreatic fibrosis. Many have blood sugars greater than 200 mg/dL arising at about 1 mo. of age. It is unclear whether infants with CF exhibit the same early abnormalities, but there is certainly evidence that we should study further. </div>
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Engelhardt shows that 42% of patients aged 1-5 exhibit abnormalities in glucose tolerance. He goes on to describes the current hypotheses to describe the pathogenesis of CFRD. Some believe that the exocrine disease in the pancreas (inability to secrete digestive enzymes), spills over to affect the endocrine function (ability to secrete the hormone insulin) of the pancreas. Others predict that insulin secretion is tied to CFTR function. I am really curious to see the results of the upcoming studies to examine this link.</div>
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Engelhardt described regions of the pancreas called islets, which contain insulin producing cells. Islets contain detectable levels of CFTR, which suggest that CFTR function may play a role in maximizing islet function. The Plenary session concluded with the recommendation that tight nutritional control may have a large impact on the progression of CFRD, and that further studies in pig and ferret models may lead to therapies that slow the beta cell dysfunction in CF. </div>
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The message that I took away from this Plenary session is that impaired insulin secretion begins early in life for CF patients, and can progress undetected by our current OGTT methods. While there are many ways that CFRD differs from type II diabetes, similar management strategies may be useful for both groups (reduced carb intake and regular exercise). It can be really tough to meet CF fat and calorie needs when you place ANY kind of restrictions on the diet, but it looks like we are going to need to get real about the amount of carbs being used to reach those dietary goals. The earlier we are able to detect, intervene, and manage glucose intolerance--the longer beta cell function can be preserved, improving blood sugar control. </div>
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Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com1tag:blogger.com,1999:blog-7535774120903384819.post-726115529851655922013-10-19T17:18:00.001-07:002013-10-20T19:20:56.154-07:00Roadmap to a Cure: Part II--Leave No Mutation Behind<div class="separator" style="clear: both; text-align: center;">
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Today started out with the second Plenary session: <b>Roadmap to a Cure: Part II</b>. The discussion was given by Dr. Bonnie
Ramsey, University of WA School of Medicine, Seattle WA. Dr. Ramsey is also the Director of the CFF
Therapeutics Development Network. She is
extremely smart and we are all lucky she has dedicated her career to CF. <o:p></o:p><br />
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Dr. Ramsey’s talk went into detail about how the CFF is
working to “leave no mutation behind.”
She talked about what was learned in the process of getting a successful
FDA approval for Kalydeco and how we can use that “roadmap” to guide us toward
successful treatments for other mutation classes. I mentioned in the day 1 summary that knowledge of your
personal mutations and their functional class will be crucial to take advantage
of genetic modifying treatments like Kalydeco.
In the spirit of discovery, it is important to mention that the CFF has
a free program to identify unknown mutations in patients called MAP—The Mutation
Analysis Program. If you have a CF
diagnosis, but only 1 known mutation, the CFF will sequence your genome for
free and find it! This is so incredibly important. Standard panels to screen for CF usually include the most common 23-26 mutations. NONE OF THE OTHER GATING MUTATIONS (other than G551D) ARE INCLUDED IN THE SCREENING PANELS! If you still have an unknown mutation, it could potentially be in the gating class, and Vertex has already applied to the FDA to expand Kalydeco access to these patients! Imagine what a pleasant surprise it would be to learn that your rare unknown mutation has a gating defect and you could soon begin taking and benefiting from Kalydeco!!! I hope everyone with
an unknown mutation will take advantage of this. <a href="http://www.cff.org/LivingWithCF/AssistanceResources/MAP/">http://www.cff.org/LivingWithCF/AssistanceResources/MAP/</a> If you know your mutations, but are unsure of
which class they fall into, you may find that information on <a href="http://cftr2.org/">http://cftr2.org/</a>. Another valuable explanation of
mutation classes and their dysfunction can be found at <a href="http://www.cftrscience.com/">http://www.cftrscience.com/</a> I wrote a blog in 2011 about mutation classes: <a href="http://luckycfmom.blogspot.com/2011/11/mutation-matters.html">http://luckycfmom.blogspot.com/2011/11/mutation-matters.html</a> Of course, the CF clinic team may also be able to offer information on
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CF mutations are divided into 5 basic classes based on the
nature of CFTR dysfunction they exhibit.
Mutations within the same class have similar cellular dysfunction,
meaning that if a drug shows a positive response with 1 mutation within the
class, there is potential that the drug may be therapeutic to the entire class.
In general, class I, II, and III are associated
with more severe disease manifestation because they exhibit little to no
functional CFTR activity. Class IV and V
mutations are associated with milder disease—patients may be pancreatic
sufficient or slightly lower sweat test scores.
In these two classes, there is a very small amount of at least partially
functional CFTR on the cell surface. There
are over 1900 CF mutations that have been discovered. You can imagine that it is going to be a
complex task to address each and every one, but the experience with Kalydeco
shows us that IT CAN BE DONE. <o:p></o:p><br />
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Ivacaftor clinical trials taught us that when approximately
30% CFTR function is restored, many clinical symptoms can be ameliorated. Kalydeco is able to reach this therapeutic
threshold for all gating mutations. I am hopeful that the FDA will give this a
quick positive ruling. Kalydeco
monotherapy may also soon be extended to children 2-5 who have G551D or any
gating mutation. The KIWI
study (Kalydeco study in ages 2-5) has officially completed enrollment. This is a 24 week study and results are
anticipated in the second quarter of 2014. <o:p></o:p><br />
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The KONDUCT study is another phase 3 trial that is already underway,
and tests Kalydeco in the R117H mutation.
Results of this study are expected by the end of the year. Right now, Kalydeco is approved to treat
about 4% of the CF population. If the
label is expanded to include all gating mutations and R117H, we can bump that
number up to about 7% of CF patients being treated with a gene modifier. I want to reiterate that these mutations were
not <i>selected </i>to be the first to be
treated—in contrast, they were treated first because they are the absolute
easiest to correct. These patients have
CFTR sitting on their epithelial cell surface, just waiting for a small
molecule like Kalydeco to come along and open that dormant CFTR channel. <o:p></o:p></div>
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There is a major focus on "fixing" the DF508 mutation, which falls into class II. Mutations in this class exhibit multiple,
complex dysfunctions within the cell. The CFTR protein is 1) misfolded,
2) thermally unstable (the protein is sort of “floppy” and often unravels at
normal body temp), and 3) also exhibits a “gating” defect. In other words, even if you were able to
correct the folding and thermal instability, you would still have a CFTR
protein sitting on the surface unable to open—like G551D and other gating mutations. To restore any meaningful function, a
combination of <i>correctors</i> and <i>potentiators</i> must be used. <i> Correctors</i> are small molecules that target
misfolding, instability, and trafficking to the cell surface (problems inside
the cell). Potentiators target the
gating defect (inability to open and close properly), once the CFTR protein
reaches the appropriate place in the cell (cell surface). Lab studies have shown that multiple corrector compounds plus a potentiator like Kalydeco, may be needed to obtain the level of clinical benefit seen in with Kalydeco in gating mutations. When you pair multiple corrector molecules together to target different problems within the DF508 protein, the amount of CFTR rescue is increased dramatically--up to 80% restored function (that is even BETTER than Kalydeco works for G551D patients!). These multi-corrector combos are still a few years out though, and I am still very optimistic that we will see an FDA approval of a first generation combination like VX-809/VX-770. There are 2 phase 3 trials moving forward right now examining optimal dosages and relative change in FEV1. The hope is that within the next several years, a drug combination will be FDA approved to treat the DF508 mutation, which will hopefully translate to treatment for all of class II. Because 50% of the CF population is homozygous for DF508 and 90% of the CF population carry at least one copy of this mutation, an effective treatment for DF508 could benefit up to 90% of the patient population. While the VX-809/VX-770 combo is currently only being tested in homozygous patients, there is the potential that many heterozygotes may also benefit to some extent from this combination. Remember, with Kalydeco and G551D, only one mutation is being treated. Heterozygotes with one copy of DF508 should be hopeful about any combinations designed to treat double DF508--especially the second generation combos, which have proven to be significantly more powerful in their ability to rescue CFTR function. </div>
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What about Class I nonsense mutations? Last year, the Ataluren studies yielded some disappointing results. They failed to meet their primary endpoint and found that there is a strong drug interaction between Ataluren and inhaled aminoglycosides (TOBI is this type of drug). Patients who were NOT taking TOBI showed some statistically significant improvement on Ataluren (5.7% increase in FEV1), but those who WERE taking TOBI showed absolutely no benefit. Last year, no one seemed willing to hypothesize on the future of Ataluren and I feared the antibiotic interaction problem might be too much to overcome. This year, Dr. Ramsey announced that there PTC Therapeutics will be moving forward in an additional phase III study to test their drug only in patients not on Tobramyacin therapy. In addition to this study, the CFF has initiated new research to address this mutation class. The CFF invested millions of dollars this year and enlisted big hitters like Pfizer to search for new molecules to treat Class 1 mutations. I understand that the Ataluren results were extremely disappointing for many--but please know that book is not yet closed! Not only is the search on for a brand new molecule to treat class 1 mutations, they are also screening compounds that are already currently FDA approved. There are already several other existing compounds that have been shown to promote translational read-through of the CFTR protein. Imagine how much time could be saved if we didn't have to start at the absolute beginning, with a brand new compound! All the human safety trials could be skipped and we could move right into end stage trials designed to prove the therapeutic effect. Plus, it seems that there may still be a chance for Ataluren to turn out some positive data from this new phase III trial. Class I--you have not been forgotten. </div>
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OK, so we have a plan for treating Class I, Class II, Class III (Kalydeco), and many in Class IV mutations (Kalydeco monotherapy or corrector/potentiator combo). This still leaves approximately 10% of the CF population with rare mutations, who may not fall neatly into one of these therapeutic classes. Many patients in this remaining 10% may have an unidentified mutation (utilize the Mutation Analysis Program to find out!), and may discover that their unknown mutation DOES actually fall into a class with an available drug. If not...there is still a plan. Yesterday, I described some techniques that have been developed to obtain a patient's own tissues to utilize for testing. Truly personalized drugs may need the answer for these patients. With the ability to obtain patient tissues for lab testing, compounds can be screened for a therapeutic effect in that individual. When an effective drug is discovered, patients would participate in a "trial of 1," where the patient serves as their own control for the study--response guided therapy. The trial of 1 concept is already being used in Denver to test whether Kalydeco might be beneficial for certain heterozygotes with splicing or other rare mutations that produce some residual CFTR function. The CFF won't stop until a treatment is developed for 100% of mutations, and they have a plan on how to make that happen. I haven't even mentioned that there are other therapies in the pipeline that are NOT mutation specific--in the realm of "gene therapy," it doesn't matter what mutation you have. Anyone with CF would benefit, no matter their genotype. By this time next year, researchers in the UK will be ready to present their data on their huge gene therapy trial. </div>
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Changing the course of the disease at a basic level is obviously an important area of focus, and could provide amazing opportunities for all patients--particularly young children/infants that are able to be placed on these interventions at an early age. That doesn't mean that we get to forget about treating traditional issues like inflammation and infection. </div>
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<b>Advancements in Anti-microbials</b></div>
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After laying out the roadmap to eventually treat the basic defect in all patients, Dr. Ramsey then turned to other areas of development in treating CF. First she discussed a new way of improving treatment of Pseudomonas infections. It has been found that there is an excessive amount of Iron in the CF lung that contributes to bacterial overgrowth and the formation of biofilms. Iron is basically food for bacteria, which makes the CF lung a smorgasbord for organisms like Pseudomonas. Trials are moving into phase 2 for a drug called Gallium nitrate, which is a molecule almost exactly the same size as iron. The idea is that when Gallium nitrate is administered, it can slip right into the place in the cell where the iron normally resides--replacing the iron. This disables the bacteria and results in disruption of the biofilm, as well as better antibiotic penetration, and better infection control. Want to know the other good news?...Gallium is already an FDA approved drug for other indications, and it is moving into phase 2 trials in CF patients now! </div>
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MRSA infection is very common, especially among CF patients in the U.S.(vs. UK). There has been some debate about how harmful MRSA infection really is, but studies have shown that patients chronically infected with MRSA live 6.2 yrs less than those who are not. In other words, they are becoming more convinced that aggressive treatment of this infection is necessary, and 3 studies are currently open and recruiting patients! If you are interested in participating in one of these trials, contact your CF center! I recommend that everyone sign up for "Clinical Trial Alerts" on CFF.org to receive the latest and greatest clinical trial news! <a href="http://www.cff.org/research/ClinicalResearch/Find/ClinicalTrialAlerts/">http://www.cff.org/research/ClinicalResearch/Find/ClinicalTrialAlerts/</a></div>
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Of course, you can also find information on clinical trials at <a href="http://clinicaltrials.gov/">http://clinicaltrials.gov/</a></div>
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They are also investigating ways to improve treatment for Non-tuberculous myobacteria.</div>
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<b>Treating Inflammation</b></div>
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Inflammation is a big problem for CF patients. Inflammation can cause cell death, and subsequently, those dead cells leave behind waste products that are harmful to lung tissue. Neutrophil elastase is one of those waste products causing damage in CF lungs. According to the Australian ARESTCF study, patients as young as 3 months old, showed elevated neutrophil elastase levels in their lungs (a way to measure the level of inflammation), even in the absence of symptoms. In other words, it is a problem that starts early in life and progresses over time. We currently have only one proven efficacious therapy for inflammation--high dose ibuprofen. </div>
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Thankfully, there are some ideas for future studies. They will be looking at compounds that might be able to "sop up" some of that damaging elastase in the lungs. In addition, the CFF has launched a Strategic Planning Initiative to evaluate more potential areas of anti-inflammation research. </div>
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<b>My thoughts on Day 2</b>: Brock and I attended workshops and symposium talks all day and there is a lot more to write about. It has been a real challenge for me to find time for all the Conference sessions, physical therapy, schmoozing with the amazing folks in attendance, and writing the blog. Basically, I don't sleep while I am here, and Brock has been so good to chauffeur me around in the wheelchair and put up with all my craziness. I feel like I still have so much to report, but I have to wrap up for now...I have a dance to get ready for! I apologize for the quality of some of these slides and hope they are all at least readable. The funniest thing about being here is that I have been recognized by the tattoo on my left foot about 25 times, "Hey, I know that foot!" No one recognizes my face, but my foot is pretty famous! I can't believe that the Conference is almost over now, and I survived! Stay tuned peeps, more to come tomorrow! <br />
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<tr><td class="tr-caption" style="text-align: center;">Stupid escalators!</td></tr>
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<o:p></o:p>Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.com4